In 2007, my rowing friend Hilbert, his son Hilbert-Jan, Boudewijn (Jeronimo), and I made a trip along the Amazon. We departed from Bogotá, flew to Letitia on the Amazon in the south of Colombia, and traveled by boat to Manaus in Brazil. From there we traveled with a van full of Brazilian gold miners through the jungle to Paramaribo (Fig. 1).
Figure 1. From Manaus in Brazil we drove through the jungle across 36 bridges to Suriname. Left: Boudewijn and Hilbert-Jan next to the van of Bryan Chin-a-Foeng.
Middle: Boudewijn with Junior, one of the gold miners. Right: Hilbert-Jan and Boudewijn swimming at Lolo Passie in Suriname.
On a previous visit to Suriname in 2005, we received a tourist poster by Paul Woei from our host couple, Dennis and Cindy Chin-a-Foeng. On it, we saw for the first time the name "La Condamine". The caption read:
“In 1744, La Condamine made a stop in Paramaribo after a long journey from the Andes down the Amazon river. Botanical specimens which he had lost on his way were replaced.” We had never heard this name before. Fascinated by the poster, we read his travelogue and two books about him. Afterwards, we decided to partially follow the route of this French surveyor and mathematician, Charles-Marie de la Condamine.
In 1743, La Condamine left Quito in the Andes and traveled to Paramaribo, the capital of Suriname, which was then still a Dutch colony. With the help of indigenous rafts and Spanish and Portuguese rowing boats, manned by indigenous rowers, he traveled down the Amazon (Fig. 2). In both Quito and the Portuguese city of Belém at the mouth of the Amazon River, La Condamine encountered the then-prevalent smallpox disease. This illness had been brought from Europe to South America by the Spaniards two centuries earlier. More than 80% of the indigenous population in the Amazon region died from it! Smallpox also ravaged Europe, where a treatment already existed: From the blisters that formed on a smallpox patient, the fluid (pus) was transferred to a small incision in the skin of uninfected people. We now know that the smallpox virus was present in the fluid from those blisters.
Figure 2. Illustrations from the book "En descendant la rivière des Amazones", by d'Alexis Nouailhat (Éditions Épigones, 1991, Bibliothèque nationale, Paris. ISBN: 2-7366-2406-4).
Top: La Condamine travels down the Amazon in an indigenous canoe.
Bottom: Inoculations against smallpox with fluid derived from smallpox blisters in Pará (Belém) at the mouth of the Amazon River.
What are viruses?
Since 1898 we know what viruses actually are, and only since 1958 do we know what they look like: They are very small packages that contain genetic information in the form of DNA or RNA, surrounded by a protective protein shell. Viruses are not cells. The difference in size and composition between a virus and cells is shown in Figure 3. Another important difference is that viruses, unlike cells, cannot grow or divide. However, viruses can enter the same types of cells from which they originated and multiply inside them.
Figure 3. Three types of cells and a virus, drawn at the same magnification.
The animal or plant cell and the yeast cell have a nucleus in which the DNA is stored.
The bacterial cell does not have a nucleus but a so-called nucleoid.
All of these cells contain a blue-colored cytoplasm mainly composed of RNA molecules, proteins, and membrane vesicles or organelles. The virus has no cytoplasm.
The double arrows indicate that a virus can be made by all three cell types, but can only enter these cells again to replicate. The diameter of a (small) animal cell is about 10 µm, that of a bacterium 1 µm, and of a virus 0.3 µm.
As we can see in Fig. 3, cells contain a nucleus with DNA.
That applies to all animal/plant cells and to all yeast cells.
Only bacteria have a nucleus-like structure called a nucleoid.
Before any of these cells can divide, the DNA must be duplicated in the so-called replication process. During this, one of the two strands of the double helix is "transcribed" into messenger RNA (mRNA) in the so-called transcription process. Both DNA replication and transcription occur in the nucleus (Fig. 4). The mRNA is then transported to the cytoplasm and "translated" into proteins in the so-called translation process.
All these processes together enable the cell to grow and divide — something viruses cannot do.
Figure 4. Three types of macromolecules or polymers: (1) DNA contains the hereditary (genetic) information. This long, thin macromolecule forms the so-called "double helix", discovered in 1952. It can be duplicated in a replication process that occurs in the nucleus (Kern") during cell growth. The genetic information is encoded in the sequence of nucleotides (also called bases or monomers), which are the colored blocks. (2) In the transcription process, DNA is copied to messenger RNA (mRNA), consisting of a single strand that is then transported to the cytoplasm. (3) In the translation process, the sequence of these bases in the RNA is translated into the sequence of amino acids, the monomers of a protein.
The chain of amino acids then folds into, for example, a spherical structure with a diameter of 0.003 µm; compare this with the diameter of a virus (0.3 µm) in Fig. 3.
If a base changes in the DNA in the cell nucleus due to a mutation (e.g., from errors in the replication process — see the colored blocks in Fig. 4), a change can occur in the genetic code that determines the hereditary characteristics of the cell. This can lead to a different amino acid being incorporated into a protein during the translation process via the altered mRNA.
This, in turn, can alter the structure and function of that protein.
What are cells?
All living organisms are made up of cells, just as a house is made up of rooms. Comparing rooms of a house with the cells of an organism reveals not only striking similarities but also fundamental differences (Fig. 5):
(1) New construction versus growth and division. Cells cannot be newly formed the way a house is built with bricks according to instructions.
Cells can only reproduce by growing and dividing from already existing cells, using the DNA found in the nucleus. Of course, there was once a first cell, but how that happened long ago is still largely unknown.
So far, scientists have not been able to create a living cell in a laboratory solely from separate macromolecules.
(2) Building in air versus assembling in water. Rooms are built by a mason in the air, while cells can only exist and grow when surrounded by water.
Houses are built with bricks made from sand and gravel, and energy (electricity). An important building block for cells is structural protein, composed of chains of amino acids linked together using chemical energy, which then fold into a protein. In water, individual proteins can come together and form larger structures through a process called self-assembly.
While bricks are almost all the same, proteins, in contrast, are very different in shape, size, and function. A second type of protein (see Fig. 4) are enzymatic proteins or enzymes, which can be compared to small machines or devices found in a house. Depending on the types of proteins encoded in the nucleus and produced through the translation process, cells acquire different functions — such as blood cells, muscle cells, or brain cells.
(3) Instructions and genetic information. In a house, the blueprints for building all the rooms may be stored in just one room. In an organism, every cell contains a nucleus with the same set of chromosomes.
These chromosomes contain the DNA packed with the genetic information for producing proteins.
(4) Expansion versus growth and division. A house can only be enlarged by adding rooms. An organism can grow — surrounded by water — because the cells grow and divide, producing two daughter cells.
(5) People with machines versus organelles and enzymes. In the rooms of a house, people live and often keep small devices or machines in workspaces or closets, like scissors (cf. the nuclease enzyme that cuts DNA), a bead
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Figure 5. Similarities and differences between rooms and cells. See text.
spinner (cf. the polymerase enzyme that makes DNA or RNA polymers), a 3D printer (cf. the ribosome that makes proteins encoded by mRNA), or a meat grinder (cf. the proteasome that breaks down proteins). In cells, other “cells” can live; this is called symbiosis. Bacteria and green algae, for example, are believed to have evolved into mitochondria that produce chemical energy, and, in plant cells, into chloroplasts that produce sugars and oxygen in the so-called photosynthesis process. These have become organelles that still contain DNA.
Discoveries of cells, DNA, proteins, and viruses
In Figure 6, the history of important biological discoveries is shown.
It begins with the visualization of cork cells (1665) and bacteria (1674) using microscopes. Then the proof of germs (1877) and the discovery of viruses (1898), the DNA double helix (1952), and the large proteins that form antibodies (1959). Finally, the development of molecular biology (1964), which made it possible to develop mRNA vaccines against the SARS-CoV-2 virus (2020), which caused the COVID-19 pandemic (2020–2024).
In Figure 7, the history of viral infections (e.g., smallpox) and vaccinations is depicted. During his stay in South America (1735–1744), La Condamine encountered smallpox epidemics. In Europe, the smallpox virus was combated with “vaccines” from cowpox, which caused less severe illness in people. Thanks to the development of real vaccines, first the poliovirus (1952) and later the smallpox virus (1980) were eradicated worldwide.
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Figure 6. History of biological discoveries.
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Figure 7. History of viral infections and vaccinations.
What happens during a viral infection and a vaccination?
When viruses enter our body and our cells during an infection (e.g., via the nasal mucosa; see Fig. 8), we can become ill. At the same time, our body recognizes the viruses as foreign proteins (so-called antigens), against which our immune system — present throughout the body — reacts with an immune response.
Figure 8. During infection, the virus attaches via its spike protein to a receptor protein present on the (nasal) mucosa. Entry occurs via the process of endocytosis.
Both after infection and after vaccination, an immune response is triggered throughout the body, specifically targeting the spike protein. In this process, white blood cells (lymphocytes: T and B cells) are activated by interferons, and plasma cells produce antibodies.
The antibodies bind to the virus's spike proteins, preventing them from attaching to receptors and entering our cells. The various cells and viruses are not drawn to the same scale.
This means first of all that white blood cells or lymphocytes are activated by viral proteins (e.g., the spike proteins on the outside of the SARS-CoV-2 virus) to secrete signaling proteins (interferons) (see Fig. 8).
These proteins then activate other white blood cells (T and B cells) that produce antibodies (IgG; IgM) against the spike protein (the antigen).
These large proteins, discovered in 1959 (see Fig. 6), inactivate the virus so that it can no longer use the spike proteins to enter cells and replicate.
Moreover, they mark the virus so it can be engulfed and broken down by T-cells. All these processes contribute to the severity of a viral infection, during which many cells in different organs can be destroyed by the viruses.
In vaccination, for example with the mRNA vaccine against the SARS-CoV-2 virus, virus-like fat droplets are injected into the bloodstream.
These droplets contain mRNA that codes for a piece of the spike protein.
This also induces the immune response, resulting in the production of antibodies against the spike protein. Unlike a viral infection, no cells are destroyed in this case.
Regarding the origin of the COVID-19 pandemic and the SARS-CoV-2 virus, scientists propose two possibilities:
(1) The lab-leak theory, where one of the many studied SARS viruses may have escaped (or been deliberately released?) from the Wuhan Institute of Virology (WIV). China's refusal to grant access to laboratory data fuels the suspicion of a cover-up of a possible lab accident in which researchers were infected. Due to the lack of lab data, this theory is difficult to verify further.
(2) The natural-origin theory, in which the virus, through mutations, crossed the species barrier between animal and human (a so-called zoonotic transmission). Thanks to much recent research in laboratories around the world, this theory is increasingly supported. In relation to preventing future epidemics, it is important to understand the origin of SARS-CoV-2.
From a medical standpoint, it is essential that information about viruses and vaccines is improved so that more people gain enough trust to get vaccinated.
This brings me back to the beginning of this story:
How did it happen that La Condamine had so much trust in the then-used method of inoculation with fluid from the pox of sick people?
When he had reached the mouth of the Amazon at Belém on his return journey, a smallpox epidemic had just broken out. He couldn’t travel on for a long time because no Indigenous rowers were available. While waiting there, he noticed that Indigenous people who had just come from the jungle contracted smallpox earlier and died from it more often than those who had already been living for some time with the Portuguese missionaries and had been vaccinated (see Fig. 2). When he finally was able to leave a month later with 22 Indigenous rowers, he still wasn’t entirely sure whether the inoculations helped. Did he get vaccinated himself? We only know that later in Paris, as a well-known figure, he was publicly vaccinated as a major advocate of this new treatment method.
Glossary
• Amino acid: Building block or monomer of proteins; a chain of amino acids forms a protein (Fig. 4). A cell produces 20 different amino acids. An average-sized protein consists of about 300 amino acids.
• Antibody: Protein produced by the immune system that binds to viruses or bacteria to neutralize them.
• Antigen: Foreign protein or molecule that triggers an immune response in the body. For example, the spike protein of the SARS-CoV-2 virus.
• Bacterium: Single-celled microorganism without a nucleus; sometimes causes infections. Often rod-shaped.
• Chromosome: Structure in which the long DNA molecule (the double helix) is wound around clusters (so-called nucleosomes) of various proteins, the histones. This compacts DNA into "manageable" bodies.
• Cytoplasm: Viscous fluid in the cell where biochemical processes occur (e.g., translation) and where the organelles are located (Fig. 3).
• DNA: Abbreviation of deoxyribonucleic acid. Carrier of genetic information in cells. A polymer consisting of two chains of nucleotides (monomers, also called bases), twisted around each other to form the famous “double helix” (see Fig. 6). See also polymer. Thanks to the duplication (replication) of this structure, genetic information is passed on to daughter cells.
• Endocytosis: Process by which a cell engulfs substances or particles (like viruses) by enclosing them in its membrane.
• Enzyme: Protein that accelerates chemical reactions without being consumed (comparable to a catalyst). Compared to small machines in Fig. 5.
• Epithelial cells: Cells that line and protect various organs and cavities in the body.
• Gene: Segment of DNA that codes for a specific protein. The sequence of nucleotides determines, after translation, the sequence of amino acids in the protein. Three nucleotides form a so-called codon that specifically codes for one of the 20 amino acids.
• Genome: The complete set of genetic information (DNA or RNA) of a cell or virus.
• Immune system: The body’s defense system against pathogens like viruses and bacteria. It is activated by interferons.
• Infection: Invasion and multiplication of microorganisms or viruses in the body.
• Interferons: Small proteins (a type of cytokine) made by white blood cells (lymphocytes) and naturally present in the body. They act as signaling molecules that activate our immune system and initiate the immune response (see Fig. 8).
• Lymphocyte: White blood cell involved in the body’s immune response.
• Membrane: All cells (and organelles) are surrounded by a protective structure made of fatty acids and proteins. The fatty acids form a double layer with the tails inward and the heads outward (toward water). Compare with a soap bubble, where the tails point outward (air) and the heads inward.
• Mitochondrion: Organelle that produces chemical energy by burning nutrients; the “power plant” of the cell. This organelle still contains DNA as a result of its symbiotic origin from bacteria.
• Monomer: Small molecule that can connect to form long chains or polymers, such as DNA, RNA, or protein (see Fig. 4).
• mRNA (messenger RNA): Molecule that transmits genetic information from DNA in the nucleus to ribosomes in the cytoplasm, where protein production takes place.
• Mutation: A change in the DNA code that can affect the properties of a protein.
• Nucleotide: Building block or monomer of DNA and RNA, consisting of a base, sugar, and phosphate group. There are 4 different monomers — see the colored blocks in Fig. 4.
• Organelle: Membrane-bound vesicle in the cytoplasm of “higher” cells. They have specific functions, such as energy production in mitochondria or protein synthesis or virus production in the endoplasmic reticulum. Mitochondria contain DNA because they originated from bacteria (symbiont theory).
• Polymer: A large molecule (macromolecule) consisting of a chain of many small units called monomers. The unit of DNA or RNA is the nucleotide or base; the unit of protein is the amino acid (see Fig. 4).
• Protein: The most important macromolecule that makes up cells. There are many types of proteins, differing in size, shape, and function. Each protein is formed by a chain of amino acids linked together by ribosomes in the so-called translation process. The amino acid sequence is determined by the genetic code in the mRNA (see Fig. 4).
• Receptor: Part of a protein on the cell surface that detects and binds to signals or molecules like viruses.
• Replication: The process by which DNA is duplicated to enable cell division or virus multiplication.
• Ribosome: Protein synthesis factory. A complex of dozens of ribosomal proteins and ribosomal RNA molecules, about 25 nm in diameter. Every growing cell contains large numbers of these factories in the cytoplasm; in the bacterium of Fig. 3, more than 10,000!
• RNA: Abbreviation of ribonucleic acid. See mRNA.
• Spike protein: Protein on the surface of coronaviruses (e.g., SARS-CoV-2) that helps them enter cells by binding to the ACE2 receptor of epithelial cells (Fig. 8).
• Transcription: The copying of one of the DNA strands into mRNA as the first step in protein synthesis. Takes place in the cell nucleus.
• Translation: The process of translating mRNA into a chain of amino acids by ribosomes, as the second step in protein synthesis. Takes place in the cytoplasm.
29 juni 2025
With corrections and suggestions from Lidie.
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