Lungs

Lungs are incredibly complex networks of ducts and sacs (bronchioli and alveoli) that pull in air from the outside along 2,400 kilometres of ducts, to exchange oxygen for carbon dioxide and water. We breathe in oxygen, and breathe out carbon dioxide and water.

Without your lungs, you would die almost immediately. Try breathing out, then hold your mouth and nose closed. It's not easy. Your body wants air, and the lungs are the way to give it waht it wants.

The lungs can be damaged through disease or pollution. They're protected by the rib-cage, so generally don't suffer from physical damage.

The most common diseases in the lungs are pneumonia, chronic bronchitis, cancer.

Bronchitis and cancer are talked about elsewhere in this book. Generally, to avoid those diseases where lungs are concerned, do not smoke or be around smokers, and avoid air-polluted areas.

Pneumonia is the name for a group of diseases with the same major symptom - inflammation of the alveoli. Because there are many different diseases, there is no single cause - pneumonia can be caused by viral, bacterial, fungal vectors or even by parasites. The most common infections are viral and bacterial.

To avoid pneumonia, don't smoke, avoid polluted air, and vaccinate yourself and your family.

History

The purpose of the lungs has been known in a way for a very long time. Hippocrates and Plato in the 4th century BCE said that the lungs were for absorbing "heat" from the air and carrying it into the left heart, to balance the humours. Plato said "As the heart might be easily raised to too high a temperature by hurtful irritation, the genii placed the lungs in its neighbourhood, which adhere to it and fill the cavity of the thorax, in order that their air vessels might moderate the great heat of that organ, and reduce the vessels to an exact obedience".

It was believed at the time that everything was made of four elements, fire/earth/air/water. The difference between living things and non-living things was a "vital spirit" which was made of air. The belief was that the lungs breathed in air, which was transported from the lungs to the heart, which converted it to vital spirit for the body to use. Erasistratus (304BCE to 250BCE) was a big promoter of this idea.

Niccolo Massa in 1559 said "The function of the lung is to cool the heart with its intake of air".

These ideas were part of the foundation of western medicine, written down and codified in the 2nd century CE by Galen, and believed correct to the point that anyone suggesting they were even slightly wrong was shunned.

An early critic, although more than a thousand years later, was the Islamic scholar Ibn al-Nafis, who argued in the 13th century with Galen's statement that blood passed throught the center of the heart through "invisible pores", although he reaffirmed Galen's discovery that blood passed from one side to the other through the lungs. The first European scholar to also state this was Michael Servetus, 200 years later. He was charged with heresy by the Catholic and Calvinist churches for this and other things and they burned him at the stake.

Galen's hold on medicine started to shake when Andreas Vesalius published his De Humani Corporis Fabrica in 1543. This founded the modern science of anatomy. You can't argue with actual observation - if someone says one thing, but you can see that it is another, do you believe the words or your own eyes?

Another later critic was William Harvey, who said in 1653 that "The lungs make the spirits and indicate the nourishment wherefore more worthy than the liver if honor is judged by benefit", which countered Galen's insistence that the liver was the most important organ in the idea, and also which suggested that the lungs, not the heart, created the "living spirit" - oxygen had not been discovered at this time, so it was still unknown what the lungs were extracting from the air.

Harvey made an observation that it was "altogether incongruous to suppose that the lungs need for their nourishment so large a supply of blood". We now know that thhe blood for the lungs was not just to nourish it, but also because the blood itself needed to be "nourished" by loading up on oxygen.

Disease was thought to be something that affected the whole body and was a result of an imbalance of the "humours". However, around the beginning of the 16th century, Paracelsus pointed out that some diseases are isolated to specific organs. For example "miner's sickness", which is a catch-all term for a number of diseases including silicosis of the lungs.

In the early 1800s, tuberculosis was one of the biggest killers on the planet, claiming 25% of all deaths. It only causes 2.43% now. In 1822, a surgeon named James Carson of London said that if tuberculosis were ever to be cured, it would be by mechanical means. We prevent TB from taking hold these days by making sure the population is vaccinated against it. The TB vaccine was not invented until nearly 100 years after Carson's prediction.

A number of surgeries were performed on or around the lungs in the 19th century. A big problem with treating the lungs with surgery is that the thorax is protected by ribs. In order to get at the lungs, you must cut the ribs out of the way, which also allows you to make space in the chest if it is needed (to reduce pressure, for example). This is known as a thoracotomy.

In 1869 (Gustav Simon) and 1879 (Jakob August Estlander), thoracoplasties (removal of ribs) were used to treat empyema thoracis (infection in the space around the lungs). The earliest mention of this kind of precedure is from Hippocrates 2000 years ago for exactly the same reason.

Thoracoplasties were the main treatment for pulmonary tuberculosis and empyema all the way into the 1950s. Mostly, thoracoplasty is now only performed to help control lung cancer.

These days, we have tried and tested methods for cutting into the chest and lungs without killing the patient, but it hasn't always been that way. Celsus describes in his book "De Medicina" (approx 40AD) that "as soon as the knife really penetrates to the chest, by cutting through the transverse septum, a sort of membrane which divides the upper from the lower parts (the Greeks call it dia/fragma), the man loses his life at once".

Transplants

The first lung transplant was performed by Vladimir Demikhov on a dog in 1956. Vladimir invented the word "transplantology" and is considered one of the most important pioneers on the field. I think of him as a mad scientist. he was the first to do a lot of transplant types, including transplanting the head of a dog onto the body of another dog. Impressive, but very very creepy.

The first lung transplant in a human was performed in 1963 by Dr. James Hardy of Jakson, Mississippi, who transplanted a lung into 58-year-old John Russell who had squamous (flattened) cell carcinoma, emphysema of both lungs, recurring pneumonia, and kindey disease. The patient was serving a life sentence in prison for murder, and it was suggested to him that volunteering for the surgery might help his sentence.

The tranplant went perfectly, and the patient started breathing with the new lungs immediately. However, he died 18 days later of kidney disease. Dr Hardy's transplant was a success in that the patient didn;t die of complications to do with the surgery itself, however its long-term success can't be measured.

Within the next ten years, about 36 lung transplants were performed world-wide. Most of the recipients died within days, with only two surviving more than a month.

The main issue in lung transplants is poor healing of airway anastomosis - where the new lung is connected to the existing airway. The difficulty is that the lung is the only organ which does not heal its arterial system quickly. It can take up to four weeks for repair to be detected, so the suturing around the join needs to be done carefully. A study in 2016 discussed the various suturing metehods and their success percentages, showing with some suturing methods, airway complications can happen 41.1% of the time, while with others it can be as low as 2.1%.

The survival rate in lung transplants is not high, but has improved in recent years. The current median life-span after a transplant is 5.8 years, vs a median of 4.2 years in the 1990s. The main determinant of the life-span is not the lung transplant itself, but the underlying reason for the need of a transplant in the first place.

In order to receive a lung for a transplant, someone must die, and the deceased person's lungs must be a biological match for the patient. Otherwise, the patient's body may reject it, killing the patient.

In August 2018, it was announced that a team at the University of Texas Medical Branch had managed to remove a lung from a pig, strip it down to just the protein structure, then seed that structure with cells taken from another pig which then received the "new" lung. This bypassed the biological compatibility issue altogether.

Using that method, we increase the number of possible donors, as every person that dies can now be harvested for lungs regardless of biological compatibility. It may even be possible to 3d-print the protein scaffold of the lungs and use that completely new structure as the basis for the new lung, thus bypassing the need for anyone to die first.

It is expected that humans can use this technology within 5-10 years.

Artifical Lungs

The lung is a machine which removes carbon dioxode from blood and infuses the blood with oxygen. Because we know what it does and how, we can build machines that do the same thing.

In 1812, Julien Jean César Legallois suggested that it might be possible to create an artificial blood circulation which could keep decapitated bodies or heads alive. After a lot of animal experiments, he succeeded in an experiment where he decapitate a rabbit and managed to keep its body alive for some minutes by simulating the circulation of the blood and air using syringes.

In 1858, Mauritian physiologist Charles-Édouard Brown-Séquard demonstrated that the severed limbs of guillotined people could be kept viable for hours after death by infusing fresh oxygenated blood. He used his own blood for this experiment. To prevent the blood from clotting, he whipped it while it was clotting and removed and cleaned the fibrin threads that formed before the blood was injected into the limb. Brown-Séquard was another mad scientist. He once varnished his own skin to figure out what sweating was for and had to be revived by a student (who had to sand the varnish off... and then wondered aloud if he had saved a crank), ingested the vomit of cholera patients to show that laudanum would prevent him from contracting it (he nearly overdosed). He would swallow sponges with strings attached, to attrach stomach acids that he would then pull out and study. Most apt for this book, at the age of 72 he announced that he had dicovered an elixer of youth and immortality - extracts of guinea pig and dog testes mixed with seminal fluid and testicular fluid, all to be injected into the arm. It is believed that the effect he recorded in The Lancet was due to injection of testosterone, and not youth.

The first machine designed to remove blood from the body, oxygenate it, and return it, was built in 1885 by Maximilian von Frey of Austria, who built the machine at the university of Leipzig in Germany. However, there was a problem in that the blood quickly coagulated when removed from the body. It wasn't until 1916 that the drug heparin was discovered, which thins the blood and helps prevent coagulation.

The next step forward was in 1926 when the Soviet scientist Sergei Brukhonenko developed a device that he called the "autojector", which used the excised lungs of an animal as the oxygenator, and two pumps - one to deliver venous blood to the animal lungs, and the other to pump the blood back out to the patient. In the experiments, the patients were dogs. The recorded experiment on November 1st 1926 involved stilling the heart of a dog and then keeping the dog alive afterwards using the device for blood circulation and for exygenation. The experiment ended after two hours when the dog had a sudden massive bleed from a mammary artery. Sergei wrote "further improvement of the technique is necessary for its practical implementation".

He expanded on his reasearch into blood circulation and oxygenation. In 1926, Sergei kept a decapitated dog's head alive, showing that it was aware of the environment, and could swallow cheese given to it.

John Heysham Gibbon was inspired by the death of a patient to work on making heart-lung bypass work in humans and started building his machine in 1934. By 1942, he was able to keep cats alive.

In 1952, Gibbon was ready to use the machine in an actual surgery. He operated on a 15-month-old girl diagnosed with an atrial septal defect. Hoewever, once the surgery had begun it became clear that the problem was completely different - left-to-right shunt through a large patent ductus arteriosis. Unfortunately, the child died on the operating table.

In 1953, he performed the first successful open-heart surgery using his heart-lung machine. The patient, an 18-year-old girl with a large defect in the heart. She left the hospital two weeks later and lived another 30 years, making this a phenomenal success.

Gibbon's design was similar to Max von Frey's, in that they were both "direct contact" oxygenators, in which the oxygen is pumped directly into the blood. The issues that von Frey noted were not solved - blood streaming, foaming and clotting were still issues, and much of Gibbon's machine was devoted to cleaning the blood. This was not sustainable, and each surgery had to be performed quickly.

A better design was necessary, though, in order to allow longer bypasses for patients that needed them.

In 1955, Willem Kolff invented an artificial lung that was "cheap, disposable and simple enough to be mass-produced". The method used was based an observation that Kolff had made regarding how gases can be absorbed into a liquid through a membrane.

Coincidentally, Dr Ted Kolobow was working on identifying membranes that were useful for this purpose, leading to a paper that he presented at ASAIO (American Society for Artifical Internal Organs) in 1955.

Kolobow was inspired by Kolff's design and improved on it by creating a spiral membrane that provided a large surface area and very quick oxygenation, with little-to-no damage to the blood.

Over the next two decades, Kolobow improved his artificial lung design. At one point, he needed a certain plastic in order to make a flexible catheter. The manufacturers of the plastic refused to give it to him, in case of legal repercussions. Kolobow went out and bought a few bras, melted them down with a solvent, and created his catheters from the resulting compound.

The method, where blood is treated by oxygenating it through a membrane outside the body, was named ECMO (ExtraCorporeal Membrane Oxygenation).

In 1968, and 1969, Kolobow and his team had a few set-backs where surgeries using his devices resulted in failures, but in each case, it was other causes that killed the patients. It is unfortunate, but in order to need an artifical lung, a person needs to be very sick to begin with, so there is always a risk that even with a perfect heart-lung machine, the patient may still not survive.

By 1970, Kolobow was able to keep lambs on total by-pass for a whole week, and in 1971, he demonstrated 16 days on a venovenous bypass (from the vein, not from the artery).

Over the next decade, ECMO was taken up by other teams of surgeons successfully, leading to a number of good stories. In one case, an 11-year-old with bilateral pneumonia was kept on a bypass for 10 days. 6 months later, the boy was participating in sports events again, showing that ARDS (Acute respiratory distress syndrome) could be treated and the lungs could recover completely..

ECMO is the most used method these days to bypass the lungs and provide oxygen to the blood, but it still requires that the patient be attached to a large external machine that effectively keeps them bed-bound.

In 2017, a wearable oxygenator was announced by Dr William Federspiel of the university of Pittsburgh. his team published a paper in November describing 6 hours of portable bypass on a sheep, and they say they have since demonstrated it working for five days. The device still needs an external source of oxygen, though, so the human patient would need to wheel around a canister. However, they are working on an even-more efficient device that can extract oxygen from the air itself.

Conclusion

We are now at a stage where people can live indefinitely without lungs by using bypass machines and ECMO, are close to providing portable machines for this purpose, and if replacement lungs are preferred to a machine, it is now possible to convert any recently dead person's lungs into a viable transplantable organ, and it may soon be possible to "print" transplantable lungs.