The history of artificial blood: how donors became dead, bulls and whales

Today in Russia is celebrated the National Day of the donor, initiated in honor of the event that occurred on April 20, 1832. On that day, the Petersburg obstetrician Andrei Wolf for the first time successfully performed a blood transfusion to a woman in labor with bleeding.

Moscow alone needs more than 200 liters of blood every day. On average, in the capital alone, up to 50 thousand liters of donated blood components are poured over a year - the rest is “filled up” from other regions of Russia. Not to say that somewhere in the country there is a large concentration of donors - to meet the total need, it is necessary that there are 40–60 people for every thousand population, but this figure is lower and does not grow over the years.

Through Welcome Mail.Ru we regularly talk about charity projects in which everyone can take part - including as a donor. But since there is not enough blood from a “natural” source, it means that you need to look for alternatives. We will understand where its unlimited reserves should be hidden.

Safest blood

Let's start with the fact that people use donor help in the absence of another. The very same blood from the donor can be a source of many dangers. Sometimes people are carriers of all infections, unaware of it. Rapid analysis checks the blood for AIDS, hepatitis, syphilis, but other viruses and infections can not be immediately detected, if the donor himself does not know about them.

Despite protective measures, various viruses are often transmitted along with blood. For example, herpes, cytomegalovirus, papillomavirus. Hepatitis is sometimes transmitted because tests can detect the presence of hepatitis only a few months after it enters the blood.
Fresh blood can only be stored for 42 days (approximately) and only a few hours without refrigeration. US statistics say that about 46 people die there in one day due to blood loss - and this is another reason why scientists (not only in the States) have been working for decades to find a suitable blood substitute.

Artificial blood would save all problems. Artificial blood can be better than real. Imagine that it is suitable for patients with any group, is stored longer than normal blood and in more benign conditions, produced quickly and in large quantities. In addition, the cost of artificial blood can be made lower than the cost of blood from donors.

Hemoglobin crisis

Attempts to create artificial blood have been going on for about 60 years. And if we take as a basis the experiments of the Soviet surgeon Vladimir Shamov on cadaveric blood transfusion, first conducted in 1928, it turns out that the path to blood transfusion not from ordinary donors goes back almost 90 years.

Cadaveric blood does not clot due to the absence of fibrinogen protein in it, does not require the addition of a stabilizer for storage, and can be transferred to a patient with any blood type. You can get it quite a lot - one corpse on average allows you to prepare 2.9 liters of blood.

In 1930, the Soviet surgeon and scientist Sergei Yudin first used the clinic for blood transfusions of suddenly dead people. Subsequently, the experience gained was successfully applied during the Great Patriotic War, when blood obtained from the dead often became the only chance for survival of wounded soldiers.

The first, relatively successful experiments with synthetic blood began in the 80s of the last century, when scientists tried to solve the problem of delivering oxygen to organs. Artificial cells were made from purified human hemoglobin, an oxygen-carrying protein. However, it turned out that hemoglobin outside the cell interacts poorly with organs, damages tissue and leads to vasoconstriction. During the clinical trials of the first blood substitutes, some patients suffered a stroke. The experiments did not end there, it was just that hemoglobin molecules in blood substitutes were coated with a special synthetic polymer.

Blood. Just add water

Protected molecules are a powder that can be used anywhere by flooding with water. Synthetic cells can be used with any type of blood and stored for a long time at room temperature. However, they will not help with severe blood loss and support the patient only until the moment when a real blood transfusion from the donor is done.

In another study, perfluorocarbons were used instead of hemoglobin. These are hydrocarbons in which all hydrogen atoms are replaced by fluorine atoms. They are able to dissolve a large number of different gases, including oxygen.

In these bottles - Oxycyte, white artificial blood, consisting of several perfluorocarbons

A hemoglobin substitute based on Fluosol-DA-20 perfluorocarbon was developed in Japan and first tested in the United States in November 1979. It was first received by patients who refused blood transfusions for religious reasons. From 1989 to 1992, more than 40,000 people used Fluosol. Due to difficulties with the storage of the drug and the high cost, its popularity has declined, and production has been closed. In 2014, the Oxycyte perfluorocarbon compound appeared, but the tests were curtailed for unknown reasons.

An attempt was also made to create a blood substitute based on bovine hemoglobin. Hemopure oxygen transporter was stable for 36 months at room temperature and compatible with all blood groups. Hemopure was approved for commercial sales in South Africa in April 2001. In 2009, the manufacturer Hemopure went bankrupt, failing to obtain permission for clinical product testing in humans in the United States.

The thorny path of imitators

The application of a polymer coating on hemoglobin molecules is a painstaking process that does not reduce the cost of artificial blood. In addition, hemoglobin is only part of the problem. Each set of cells (erythrocytes, platelets and leukocytes) has its own significance for the organism. Developments in the field of blood substitutes are mainly aimed at reproducing only one function of the blood: supplying tissues with oxygen. In other words, the area outside of the oxygen-transport red blood cells is an impassable thicket of hazards for scientists.

As the biophysicist Mikhail Panteleev described in an article about the problems of artificial blood, in recent years it has been possible to make significant progress in the field of platelet imitation, which is responsible for the elimination of injuries due to minor bleeding. Scientists take a liposome or nanocapsule hundreds of nanometers in size and insert the necessary proteins into it. Artificial platelets can be fixed for the few platelets that a person still has with a strong blood loss. But when the body does not have its own platelets, artificial ones will not help.

Despite the fact that artificial platelets do not have all the functions of real living cells, they can successfully stop bleeding in emergency cases.

It looks like the blood of sea worms

With the right proteins you can do a lot of interesting things. Romanian scientists from Babes-Bolyai University have created an artificial blood substitute based on iron-containing hemerithrin protein, which is used to transport oxygen to some species of marine worms. A team of biochemists from Rice University went deeper and began to use whale muscle proteins. It turned out that whales have an accumulating oxygen in the muscles myoglobin , similar to hemoglobin from human blood. Deep-sea animals, having a large supply of oxygen in the muscles, for a long time may not float to the surface. Based on the study of whale protein, it will be possible to increase the efficiency of hemoglobin synthesis in artificial erythrocytes.

Much worse things with leukocytes, which are an integral part of the body's immune system. The same erythrocytes, oxygen carriers, can be replaced with artificial analogues - for example, perftoran created in Russia. For leukocytes, stem cells didn’t come up with anything better, but along the way there were too many difficulties associated with the aggressive actions of the cells against the new host.

Nano blood

Robert Freitas, author of the first technical study of the potential medical use of hypothetical molecular nanotechnology and hypothetical medical nanorobotics, developed a detailed project for the creation of an artificial red blood cell, which he called "respirocyte."

In 2002, Freitas in the book “Roboblood” (robotic blood) proposed the concept of artificial blood, in which instead of biological cells there will be 500 trillion nanorobots. Fraytas represents the blood of the future in the form of a complex multi-segment nanotechnological medical robotic system capable of exchanging gases, glucose, hormones, removing waste of cellular components, carrying out the process of dividing the cytoplasm, etc.

At the time of the creation of the concept, the work looked complete fantasy, but after 15 years, that is, already now, in 2017, Japanese scientists reported on the creation of a biomolecular microrobot controlled by DNA. Japanese researchers have solved one of the most difficult tasks of nanotechnology - they provided a mechanism for moving the device through the use of synthetic single-stranded DNA.

In 2016, Swiss scientists published a study in the journal Nature Communication on the creation of a prototype nanorobots, capable of conducting operations within humans. The design does not have engines and rigid connections, and the body itself is created from a hydrogel compatible with living tissues. Movement in this case is due to the magnetic nanoparticles and the electromagnetic field.

Focusing on these studies, Fraytas remains optimistic: he is confident that in 20-30 years it will be possible to replace human blood with nanorobots that are powered from glucose and oxygen. To produce electricity from the body's glucose, Japanese scientists have already learned.

Stem cell blood

Hematopoietic stem cells derived from bone marrow give rise to all types of blood cells.

In 2008, it was possible to establish the production of blood cells from iPS cells (capable of acquiring different functions) obtained from human organs. Stem cells were the best sources of red blood cells.

In 2011, researchers from the University of Pierre and Marie Curie (France) conducted the first small transfusion to volunteers of red blood cells grown in the laboratory. These cells behaved in the same way as normal red blood cells, with about 50% of them still circulating in the blood 26 days after transfusion. In the experiment, volunteers poured 10 billion artificial cells, equivalent to 2 milliliters of blood.

The experiment was successful, but another problem arose - one hematopoietic stem cell was able to produce up to 50 thousand red blood cells, and then died. Getting new stem cells is not a cheap process, so the cost of one liter of artificial blood became too high.

In 2017, scientists from the State Donor and Transplantation Service of the National Health Service of the United Kingdom (NHS Blood and Transplant) together with colleagues from the University of Bristol conducted experiments with hematopoietic stem cells . It turned out that the earlier the cell is, the higher its ability to regenerate - so, with just one hematopoietic cell, all hematopoietic tissue in a mouse can be recovered. Scientists managed to use stem cells for the production of artificial blood at early stages of development, which finally made it possible to produce it in almost unlimited quantities.

Red blood cells created in this way at the end of 2017 will begin to be tested on people. Continuous generation of erythrocytes from suitable cells reduces the cost of artificial blood, but its future depends on passing a clinical trial.

And even after successful clinical trials, no one can replace conventional donors. Artificial blood in the first years of its appearance will help people with rare blood groups, in hot spots and in the poorest countries of the world.

Sources:

Forward Of One Of The Quarries: Artificial Blood
Artificial breeding
The Long Quest To Be Armed
What is artificial blood?
Holy grails: artificial blood