Producing Hemoglobin— Reducing blood shortages
Malaria, anemia, sickle cell disease. These are all diseases that require blood transfusions. But when we look at one of the most basic components of the human body, blood, we quickly come to the realization that insufficient blood supply is one of the most overlooked problems, causing so many deaths all over the world.
Blood is universal, we all need it to live. But, the world has a blood shortage. Of 180 countries surveyed, 107 of them didn’t have enough blood to meet their needs.
And even while people are donating blood, there still isn’t enough supply. A big part of this is because the world is relying on donations, which is an ineffective method of collecting blood.
Even with the lack of donors, other problems still persist such as blood type incompatibility, short shelf life, and risk of bloodborne diseases (HIV & Hepatitis B). Well, what if we could just create blood instead?
The science behind blood
Blood is what carries oxygen and nutrients to our cells. Our blood flows through the body and is pumped by the heart. But it’s got to be made up of something... right?
When we think of blood, we think of red blood cells. But there’s more to blood than just the red blood cells. There are also white blood cells, and platelets, and plasma.
The total amount of blood that a person needs is approximately 6o milliliters per kilogram of body weight. This means that if we look at the amount of blood that’s available in hospitals to patients that need it, it really isn’t enough.
Blood Types
Which type of blood would we create? It isn’t feasible to create many different types as opposed to O-Negative, the universal donor. The reason that O-Negative is the universal donor is that people with this blood type’s blood cells don’t have any A, B, or Rh antigens. Those antigens could be dangerous to people with different blood types.
Now that we understand which blood type we would want to replicate, we need to understand the components and proteins in the blood.
If we could reproduce hemoglobin (an essential gene in the human body which is carried by red blood cells), we would be able to increase the availability of blood to the world.
Hemoglobin, The Basics
Hemoglobin (also called haemoglobin) is made up of 2 similar proteins that stick together called heme and globin. That means that to produce hemoglobin both proteins need to be synthesized. If both proteins aren’t present, the hemoglobin isn’t able to pick up and release oxygen as normal.
Hemoglobin forms an unstable and reversible bond with oxygen. When exposed to oxygen, it becomes bright red, and without exposure, it is a purplish-blue colour.
It is made up of 4 polypeptide chains. Polypeptide chains are just sequences of amino acids that create proteins.
By combining dozens of amino acids to form the 4 polypeptide chains, hemoglobin is created. And every hemoglobin molecule is made up of 4 heme groups surrounding a globin group.
Heme
Heme is made up of a ringlike compound called porphyrin. An iron atom is attached and is the part that binds oxygen to the blood (so we know it’s important).
Since there are 4 heme groups in a hemoglobin molecule, and each heme group contains one iron atom, it means that there are 4 oxygen atoms in 1 hemoglobin molecule.
Globin
The base composition of a globin gene cluster can naturally vary. However, in the β-globin in hemoglobin promotes the full expression of globin genes.
Why produce hemoglobin?
Hemoglobin is essential for picking up oxygen and delivering it to the lungs. Our cells are alive because of hemoglobin, and by synthetically producing this essential protein, blood transfusions can be made more accessible around the world.
The Steps
Firstly, finding a good host.
The model yeast Saccharomyces cerevisiae is ideal as it has been sequenced previously, its genetics are easy to manipulate, and it’s easy to maintain in a lab.
Secondly, the genetic code to create hemoglobin would be added in vitro to the model yeast by using an inactive virus. This means that the part of the DNA or the “instructions” to create hemoglobin is carried by a DNA vector (the carrier).
Lastly, the heme and globin would be left to synthesize, and would “stick together” to become hemoglobin.
Key takeaways
- Hemoglobin is crucial to human cells since it carries oxygen
- If we can replicate hemoglobin, blood transfusions can become more accessible globally
- A single hemoglobin molecule is made up of 4 heme groups surrounding one globin group
- By using synthetic biology we can engineer a yeast model to produce hemoglobin
