Albumin treatment: Memorable invention of Edwin Cohn in the WW2.

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Albumin

Millions of soldiers who were seriously injured on the battlefield during World War II were saved by Albumin treatment which was invented by Edwin Cohn, an American biochemist. Albumin is the most abundant protein in blood plasma. Albumin injected into a ‘shock injury’ patient absorbs the fluid in the body tissues. Therefore, the blood vessels remain full (dilated).

The albumin solution does not flow out of the blood vessels in the body. Moreover, once obtained in pure form, albumin is stable at different temperatures. Today, the same treatment is used around the world to recover patients from severe shocks and burns caused by accidents, as well as during some heart surgeries.

Brief information: Edwin Kohn

Edwin Kohn was a notable leader in the study of proteins. After taking his Ph.D. (1917) with L.J. Henderson of Harvard and F. R. Lillie of the University of Chicago, he worked with T.B. Osborne in New Haven and S.P.L. Sorensen in Copenhagen. He initiated active research on the physical chemistry of proteins, especially on their solubility in different media and their acidic and basic properties.

He initiated and directed a major program, involving biochemists, clinicians, and many others, for the large-scale fractionation of human blood plasma. This yielded purified serum albumin for the treatment of shock, gamma globulin for passive immunization against measles and hepatitis, fibrinogen and fibrin for neurosurgery, and numerous other protein fractions of blood plasma.

Edwin Kohn Early Life

(December 17, 1892 – October 1, 1953).  Edwin was born in New York to a very respectable and wealthy family. His father had a tobacco business. Edwin and his three siblings grew up in a wealthy family. Edwin initially studied literature and art at Amherst College for 2 years; but he realized that he was more interested in science and enrolled at the University of Chicago. In 1914, he graduated with a degree in Chemistry.

Edwin was greatly influenced by the famous book ‘The Fitness of the Environment’ written by Harvard’s Lawrence Henderson. While researching at the University of Chicago, he studied the chemistry of seawater under the guidance of Henderson and Woods Hole. He received his doctorate in chemistry in 1917, and the same year he married Marian Betuer, the daughter of a prominent New York gynecologist. Edwin went to Harvard and Yale university’s for further research. Marian completed a course in biochemistry after their marriage, so she helped Edwin a lot in the lab. Later she also worked as his secretary.

Edwin Cohn's background and expertise in biochemistry

Edwin led the research on proteins in the newly formed Department of Physical Chemistry at Harvard Medical School. His favorite part of research was to study the properties of the ‘amino acids’ that make up proteins, to develop fractionation methods to isolate and purify proteins from a substance.

Leadership in protein research

In the spring of 1940, signs of a Nazi invasion of Europe were beginning to appear. At the same time, the US aid to the British Army through the ‘Plasma for Britain’ project took a different turn for Edwin Cohn’s protein research. In fact, during 1938-39, Kohn researched blood proteins and discovered that blood plasma contains many useful proteins.

He had succeeded to some extent in separating the proteins from the plasma and purifying them. He also heard that the liquid plasma produced by the US to treat war-wounded soldiers was spoiled by bacterial growth. As Edwin he was an excellent protein chemist, ‘If instead of plasma the proteins could be isolated and made into a transfusion solution, it would be more convenient to use; Moreover, there will be no risk of infection,’ he thought. 

Plasma fractionation technique and albumin

Plasma is the body fluid of living organisms, its chemistry is complex and delicate. This liquid, which looks like a clear thin tea, is composed of 93% water, 1% salts, and 6% different proteins. Edwin knew that when ethyl alcohol, a chemical solution, was mixed with plasma, plasma proteins would settle to the bottom and be separated; But after doing this, all the proteins in the plasma would gather at the bottom.

It was very difficult to separate them from each other. Edwin had to find a method that would isolate all the proteins one by one from the plasma. He found a better solution to this and from this he found the exact technique of ‘plasma fractionation’.

What is Albumin?

A type of globular protein that is characterized by its solubility in water and in 50% saturated aqueous ammonium sulfate. Albumins are present in mammalian tissues, bacteria, molds, and plants, and in some foods. Serum albumin, which contains 584 amino acid residues, is the most abundant protein in human serum, and it performs two very important physiological functions.

This protein is responsible for about 80% of the total osmotic regulation in blood. When excessive amounts of albumin are found in the urine upon clinical examination, some form of kidney disease is usually indicated. A second physiological function is that it transports fatty acids from adipose tissue to muscle. Another important albumin, ovalbumin, is found in egg white. This protein is about two-thirds the size of serum albumin, and it contains sugar residues in addition to amino acid residues.

How Cohn developed the process for isolating albumin from blood plasma?

The protein that Edwin received from the first fractionation during ‘plasma fractionation’ was fibrinogen, which is necessary for blood to clot; The latter two fractions contained proteins belonging to the ‘immunoglobulin’s’ group, which play an important role in the immune system, while the fourth fraction contained cholesterol and other immune factors. The faction that Edwin wanted was the 5th and last. It contained the essence of all his sourness and that fraction is ‘Albumin’! He isolated albumin in pure form as a white powder.

Albumin Treatment: A Game-Changer in Medical Care

Only one-fifth of the amount of albumin needed to save a patient from shock is plasma powder. Therefore, one packet of albumin would do the same work as 5 packets of plasma powder. Edwin emphasized the extraction of albumin from plasma as an emergency measure to save wounded soldiers in war. It was also important to examine how albumin was used in humans. So several young doctors in Edwin’s team began testing albumin on humans.

11 Harvard Medical School students were willing to test themselves. About 1 liter of blood was drawn from each student and then they were injected with albumin. After testing their blood samples, each student’s blood volume returned to a normal level similar to that of healthy adults after being given albumin. They did not have any other side effects due to albumin.

Albumin treatment during WWII

In 1941, there was news of the attack on Pearl Harbor. Immediately, Kohn and colleagues began collecting vials of albumin in the lab. Isidor Ravdin, a doctor at the University of Pennsylvania, was ordered by the Navy to go to Hawaii immediately, and that’s when he immediately called Edwin and asked him to bring him as many bottles of albumin as he could find in his lab.

At that time Edwin and his colleagues sent 50 bottles of albumin to Ravdin. When Ravdin reached Pearl Harbor, 4 days had passed since the bombing of Pearl Harbor. 25,000 people died in this attack. More than a thousand were seriously injured. The number of people burnt was high. The Navy hospital was overflowing with wounded. Apart from this, the barracks, mess hall and officers’ club also got the look of a hospital.

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Albumin treatment and Pearl Harbor

The doctors tried their best to treat the injured. Ravdin injected albumin into 7 of the most severely burned subjects and all of them improved. The condition of one of them was so serious that, ‘Is this treatment going to be of any use?’ Another doctor asked Ravdin; But Ravdin gave him an injection of albumin two days in a row and his health miraculously improved.

A few weeks later Ravdin came to Boston to report on albumin transfusions; By that time a total of 87 people had been given albumin. Only 4 of them experienced minor side effects. Now the government realized the usefulness of albumin. So, the government decided to produce albumin on an industrial scale.

How albumin treatment revolutionized medical care during WWII

Batches of albumin began to be produced every week. After this, the albumin was heated at 60 degrees Celsius for 10 hours. Due to this, it would become sterile. Then its purity, water absorption capacity, viscosity i.e. the stickiness of the solution and its resistance to flow, ‘light-radiating properties’ (light scattering properties) of the albumin water solution were checked and then the albumin solution was filled in a small glass vial. Edwin contacted hospital specialists, immunologists, and biochemists at several American universities to form a national movement for plasma fractionation and albumin production.

Edwin Cohn was a consultant to the Red Cross and the American Legion. Also, after each company made a batch of albumin, samples were tested in Edwin’s lab. Edwin saw to it that every minute step in plasma fractionation and albumin production had to be precise. Edwin’s lab experiments on the production of albumin were successful, and companies selected for the project set up large-scale albumin production plants. These factories were equipped with shiny steel tanks, large fridges, high-speed centrifuge machines and 24-hour on-duty security guards.

In war, the reserves of any country are diverted more towards military needs. At that time, The Arpels Company of Philadelphia was the only company manufacturing high-speed centrifuges for the production of albumin in America. This caused many difficulties in the production of albumin; But overcoming it, in November 1942, the first batches of albumin were dispatched.

Over the next 4 months, more than 10,000 vials of albumin were produced per month. Yet Edwin wanted to increase this number to 25,000 or even more. Because the demand for soldiers still could not be met. The root of this problem was in the raw material of albumin! It was impossible to get human blood as much as needed.

Ethical concerns or controversies surrounding the use of albumin treatment.

Edwin began to isolate albumin from cow’s plasma. Cow plasma was very similar to human plasma. Moreover, cow’s blood was obtained from the slaughterhouse as much and continuously as required. When Edwin separated plasma from cow’s blood and obtained albumin by fractionation technique, he also noticed that it was similar to human albumin. In April 1941, Harvard doctor Charles Janeway noticed that only one of his 30 patients who were given cow’s albumin had minor side effects.

Subsequently, 3,000 prison inmates and medical school staff were given very low doses of cow’s plasma albumin with no ill effects. Under Edwin’s guidance, ‘Armour and Company’ in Chicago began manufacturing ‘bovine albumin’ to supply the army on a large scale. As this albumin is obtained from ruminant animals like cow, buffalo, ox, it is called ‘bovine albumin.

But later there were problems. However, the results of a trial conducted on inmates at the Norfolk Prison Colony in Massachusetts were alarming. Among the 66 prisoners who were injected with albumin, 21 experienced side effects such as muscle pain, anemia skin swelling, and red spots after the injection. Unfortunately, 1 of the prisoners died suddenly on the 27th day after receiving the albumin injection.

He also had similar ‘allergic reactions’. After his autopsy, it was revealed that he died of a heart attack due to swelling of his heart. The swelling of the heart was an allergic reaction. Edwin took full responsibility for this and stopped producing bovine albumin, and immediately stopped all of his human trials.

Conclusion

Edwin Cohn’s pioneering work in developing albumin treatment during World War II stands as a testament to human ingenuity and the ability to transform scientific discoveries into life-saving innovations. His dedication to advancing medical science not only revolutionized battlefield medicine but also paved the way for numerous medical applications that continue to benefit patients worldwide. The legacy of albumin treatment serves as a poignant reminder of the profound impact that scientific breakthroughs can have on improving human health and well-being, even in the face of adversity.

 

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