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This video is brought to you by CuriosityStream.\h Sign up today at curiositystream.com/\h\h
realscience to get free access to Nebula and catch\h up on Real Engineering's Logistics of D-Day series\h\h
in time for the final episode. In 1959 the\h British Medical Journal reported on something\h\h
that had never been seen before - several patients\h with a mysterious condition, something happening\h\h
inside their blood that doctors didn't think\h was possible. Historically, we've understood\h\h
our blood types to be a constant immovable\h fact of our genetics and of our existence.\h\h
But what these doctors found were several\h definitive cases of people with an A blood\h\h
type showing signs of their blood type changing\h suddenly having red blood cells temporarily\h\h
expressing the B blood type antigen. This\h acquired B phenomenon, as it's called,\h\h
was never seen in healthy people, only ever in\h people with cancer in their stomach or intestine\h\h
or with some other condition where the integrity\h of the gastrointestinal wall was compromised.\h\h
Over time their blood type would return to\h normal, but scientists were not entirely sure\h\h
what had caused it. In 1972 detectives found\h a dismembered body in the River Thames. During\h\h
the forensic investigation one body part recovered\h was shown to have O type blood. Later, however, a\h\h
different part that had remained in the water for\h a longer period was identified as having B-type\h\h
blood. The blood groups therefore implied the two\h parts were not from the same individual. However\h\h
other evidence determined beyond a shadow of a\h doubt that the two parts did belong to each other.\h\h
This therefore raised the suspicion that the\h second part found had an acquired B-type blood.\h\h
What is the common link in these two strange\h situations? It's not a change in genetics that's\h\h
causing the blood type to change, nor is it an\h accidental introduction of a different blood type\h\h
from somewhere else. It's the work of bacteria\h -specifically a certain type of bacterial enzyme\h\h
that cleaves or alters certain blood antigens\h turning one blood type into another. For the\h\h
first time scientists realized that our blood\h types are not so immovable after all. This\h\h
acquired B phenomenon can certainly raise problems\h with typing blood for medicine or with forensic\h\h
science, but it could also hold the answer to\h a very big problem. If blood can accidentally\h\h
be transformed from one type to another, can\h it be done on purpose? Can we use this idea to\h\h
change blood types in order to create universal\h donor blood that is always so desperately needed?
Every two seconds someone in the U.S. needs blood,\h but only around 38 percent of the U.S. population\h\h
is eligible to give blood or platelets. And\h less than ten percent actually do it. And only\h\h
seven percent of the population has the so-called\h universal donor blood O negative. The red cross\h\h
reports that on average it only has about six\h units of type O blood available for every one\h\h
hundred thousand people. But more than twice\h that is needed every day. You can start to see\h\h
the problem here. There is an ever-present need\h for blood, especially universal donor blood,\h\h
and only so much available. In a previous video\h I discussed the importance of the different blood\h\h
groups and the ABO and Rh systems. The ABO system\h is the most important and your group is determined\h\h
by the presence of the antigens A and B which are\h carried on the surface of your red blood cells.\h\h
You can have type A, B, AB, or O - O meaning you\h have neither of the A or B antigens. The ABO group\h\h
antigens are sugars that work to recognize foreign\h cells in the bloodstream. The O blood type lacks\h\h
the A or B antigen and only has what is known as\h the H antigen. It's sort of like a blank or base\h\h
antigen. the A and B antigens are then attached to\h this H antigen in the A and B blood types, and the\h\h
only difference between the A and B blood antigens\h is a single sugar at the end of each structure.\h\h
People with the A antigen on the surface of\h their red blood cells will have an antibody\h\h
against the B antigen found on the B type blood\h cells. And conversely people with the B antigen\h\h
will have antibodies against the a antigens found\h on A type blood. During transfusion if the wrong\h\h
type of blood is injected the red blood cells\h in the injected blood will be attacked by the\h\h
antibodies and the recipient's blood causing them\h to clump together or agglutinate this will result\h\h
in hemolysis or destruction of the red blood cells\h which causes serious illness and can be fatal for\h\h
the recipient the rh or rhesus system works in a\h similar way if you're missing the most important\h\h
rh antigens you're considered to have a negative\h blood type rh negative recipients can only receive\h\h
rh negative blood but rh positive recipients\h can receive either rh positive or negative blood\h\h
and this is how the eight most common blood types\h are formed and because the o negative blood type\h\h
does not produce an incompatibility reaction\h in any of the eight types it's considered to\h\h
be the universal donor it's extremely valuable in\h medical situations because in a sudden accident\h\h
there may not be time to assess a patient's blood\h for its type as they're bleeding out if in doubt\h\h
o negative blood will pretty much always be a safe\h bet but o negative blood can be very hard to come\h\h
by some solutions to the blood shortage aim to\h get more people to donate others aim to improve\h\h
the logistics of blood delivery helping to get it\h to the people who need it most but even if more\h\h
people donated the treadmill of supply and demand\h is still profoundly difficult to stay on top of\h\h
and this is why the idea of creating universal\h blood has floated around the scientific community\h\h
for decades if we could turn any type of blood\h into oh blood then many complications in the\h\h
blood donation network could be alleviated\h but how far are we from it becoming a reality\h\h
in 1982 scientists first experimented with the\h idea of turning any of the [ __ ] blood types\h\h
a b or a b into o blood because the a and b\h blood types differ from the o type in a simple\h\h
sugar chain scientists believed that they could\h convert a b and a b red blood cells to o type red\h\h
blood cells by removing these extra sugars with\h an appropriate enzyme such converted o red blood\h\h
cells could then in theory be used as universal\h donor blood this procedure wouldn't affect the\h\h
rh status of the blood however but conversion\h of a positive and b positive red blood cells\h\h
would yield o positive blood whereas a negative\h and b negative red blood cells would yield o\h\h
negative blood at the time of this experiment\h there was only one commercially available enzyme\h\h
that might be able to cleave these sugars alpha\h galactosidase derived from green coffee beans\h\h
this looked promising to researchers but\h the enzyme came with several problems\h\h
it required a low ph of 5.7 to do the\h conversion which is not ideal for red\h\h
blood cells that prefer a ph of around 7.4 and\h to do it a huge amount of enzyme was required\h\h
making the process inefficient and not economical\h and most significantly it could only cleave the b\h\h
type antigen not the a this is because this\h enzyme can cleave the galactose of the b antigen\h\h
but does nothing to the n acetyl galactosamine\h of the a antigen nonetheless scientists were\h\h
able to convert b-type blood to o blood which\h was a huge milestone these converted blood\h\h
cells were shown to have a normal lifespan\h and to be well tolerated in the human body\h\h
but because only 10 percent of the population\h has b-type blood versus the 46 of the population\h\h
that has a type including the a antigen this idea\h would not be viable until scientists could find an\h\h
a cleaving enzyme therefore little more\h was heard of this technology for many years\h\h
that is until 2007 determined to find the missing\h piece of the puzzle scientists began the hunt for\h\h
a brand new enzyme and they began to look in\h the place where the reports about the acquired\h\h
b phenomenon had first alluded to the world\h of microbes if gut or river bacteria could\h\h
accidentally transform blood types maybe the\h right enzyme could be found among the millions\h\h
of microbes that live there thus researchers began\h digging through 2 500 fungal and bacterial samples\h\h
looking for an enzyme that could efficiently\h cleave both a and b sugar groups and within these\h\h
samples of bacteria an answer was indeed waiting\h for them they discovered two new enzymes within\h\h
two different bacteria one often found in bodies\h of water and one found in the human gut the enzyme\h\h
found in the gut bacteria could cleave the b sugar\h group at a ph of seven and the enzyme found in\h\h
the river bacteria could cleave the a sugar group\h after a 60 minute incubation with the appropriate\h\h
enzyme red blood cells with a b and a b antigens\h no longer expressed any of them they had all been\h\h
converted to the universal donor blood this looked\h like the answer that researchers had been looking\h\h
for for years but today this technology is still\h not in use something about this process was still\h\h
preventing it from moving into clinical practice\h although the enzyme found in river bacteria could\h\h
indeed cleave the a antigen it was still wildly\h inefficient the a cleaving enzyme was 30 times\h\h
less efficient than the bee cleaving enzyme 60\h milligrams of enzyme per unit of red blood cells\h\h
was needed to convert a to o whereas only two\h milligrams of enzyme was needed to convert b to\h\h
o and this is not a trivial difference isolation\h and purification of enzymes is a costly process\h\h
enzymes need to be optimized for stability and\h efficiency expressed in some unlucky organism in a\h\h
massive fermenter purified to an insane degree and\h then packaged handled and shipped and if the idea\h\h
is to convert all blood types to oh blood even in\h remote parts of the world the cost of needing huge\h\h
amounts of enzyme would make the whole thing\h infeasible the dream of creating a universal\h\h
blood was once again tabled but 16 years later\h scientists have become armed with new technology\h\h
metagenomic analysis historically to search for\h new enzymes researchers would have to collect\h\h
samples of microbes from the environment and then\h culture them a method of multiplying the organisms\h\h
by letting them reproduce in the lab this of\h course takes a fair amount of time and effort but\h\h
with metagenomic analysis scientists can assess\h the genetics of everything in a sample at once\h\h
and look for the desired genes because of this\h researchers were able to screen 20 000 bacterial\h\h
samples from the human gut looking for an enzyme\h that could efficiently cleave the a antigen\h\h
at first they didn't see anything promising but\h when they tested two of the resulting enzymes at\h\h
once the a antigen came right off the two enzymes\h are a type of deacetylase and galactoseminidase\h\h
and are from a bacteria called flavonofractor\h plowtai when they work together they provide\h\h
the solution that has eluded scientists for years\h and only tiny amounts are needed as little as one\h\h
milligram per unit of red blood cells versus\h the 60 that was needed in previous studies\h\h
their high efficiency means they could be cost\h effectively added to the already existing routines\h\h
of blood collection processing and storage with\h major implications for the global blood supply\h\h
typing blood could become obsolete and everyone\h who donates could become a universal donor\h\h
people with the more rare blood types won't have\h to wonder if the right blood will be available\h\h
to them and countless lives could be saved this\h breakthrough paper was only published last year\h\h
so time will tell how soon we can see this in\h the real world but there's a lot of reason to\h\h
be optimistic for now though more work is\h needed to ensure that all of the a antigens\h\h
are thoroughly removed and that the process will\h not cause any adverse effects in the recipient\h\h
and researchers also need to make sure the\h microbial enzymes have not inadvertently altered\h\h
anything else on the red blood cell that could\h cause problems but it looks like this decades-long\h\h
quest may be over and that the reality of oh\h blood synthesis is right around the corner\h\h
the blood supply chain is a complicated\h ever-moving machine it's a global treadmill\h\h
that thousands work tirelessly to stay on\h top of and never is that supply chain more\h\h
important than in times of war and examples from\h the 20th century show us exactly how true that is\h\h
during world war ii the american red cross flew\h almost 200 000 pints of whole blood from the\h\h
us to the allied forces in europe more than 50\h 000 pints of blood were needed for the soldiers\h\h
fighting during the d-day invasion of normandy\h alone and coordinating this was not a trivial task\h\h
as germany tried to conquer the continent of\h europe the allied forces became locked in a war of\h\h
force and power yes but also one of supply chain\h logistics and during the invasion of normandy\h\h
this contest came to its most important climax\h years of planning hundreds of thousands of men\h\h
thousands of ships tanks and trucks hundreds of\h gliders and airborne troops all working together\h\h
to pull off the largest amphibious invasion in\h military history an invasion that would change\h\h
the course of history forever if you're interested\h in how the allies were able to coordinate such a\h\h
massive military effort then you should catch\h up on the logistics of d-day series made by\h\h
our other channel real engineering available\h exclusively on nebula it's a multi-part series\h\h
with episodes about the logistics of close air\h support fuel supply deception tactics and more\h\h
the final episode in the series will be released\h soon detailing the famed truck convoy the red\h\h
ball express that supplied allied forces moving\h quickly through europe after breaking out from the\h\h
d-day beaches in normandy this original series\h is available on nebula which is the streaming\h\h
platform made by me and several other\h educational youtube content creators\h\h
it's a place where we can upload our videos ad\h free and a place where we can experiment with\h\h
new sometimes controversial content that wouldn't\h work on youtube there are long form documentaries\h\h
by creators like wendover productions\h original series by creators like tom scott and\h\h
collaborative series like working titles that are\h created by dozens of different creators together\h\h
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