As a liberal arts major, I am always looking for unusual, little-publicized, but nonetheless credible scientific theories. One that is widely accepted in the area of oncology is the ‘seed and soil’ hypothesis, and I will include a vigorous defense of it near the end of this post. The seed and soil hypothesis is very old (from the late nineteenth century) and very interesting; however, there are some important caveats to mention before we unpack it.
First of all, there are many different types of cancer. Therefore, there is certainly not a common explanation for how cancer spreads, and there are various causes of cancer. Additionally, when dealing with theories, there is always some ‘wiggle room.’ Not everything happens as predicted; for example, a woman with the BRCA1 or BRCA2 genes will not necessarily develop cancer.
In my lifetime, I have tried my hand at gardening. I found that some plants (particularly weeds) will shoot up virtually anywhere. For example, I can scatter radish seeds on the asphalt of my driveway, and after a rain, they will sprout, though not grow. I have successfully grown plants such as epiphytic orchids without any foundation at all—either by just sticking the roots loosely in an empty clay pot or by hanging the plant by the stem from a hook or cord and misting the root system regularly.
Then there are hydroponic plants. Cucumbers grow readily using hydroponic techniques, while carrots and potatoes are miserable failures without soil. Yes, soil. The best soils on this planet are Chernozems (a.k.a. black earth), Mollisols, alluvial soils, loam with sand, silt, and clay providing good drainage and aeration, and silt. Compost is often added to some of these for its nutrient value as well.
Most plants, however, are picky about how they are potted or planted. Tulip bulbs must not be planted upside down, and insectivorous plants need a certain pH in the soil. Some plants require a planting medium that drains quickly, while others prefer to be damp.
So, just as soil with certain characteristics is welcoming to some seeds, other soil is not. This post is about cancer “seeds,” or, more precisely, cancer cells and the organs in which they can take root when they metastasize.
Ways that cancer can spread to other organs
Single cancers spread to surrounding tissues within an organ to form tumors. This is called local invasion. After that as the cancerous cells continue to multiply, the cancer cells enter the bloodstream or lymphatic system (or both). This is known as intravasation. The circulatory system can be a dangerous environment for cancer cells. For most cancers, the cells must be anchored to receive the resources that any other normal cells need. Without these they can die. So they cannot remain free floating forever. There are also the flow dynamics in the blood which can sometimes compromise the integrity of the cells, tearing them apart.
Specially engineered viruses called oncolytics can attack passing cancer cells and that can lead to the death of the cancer cell as well. Those cells that manage to survice go on to accomplish colonization elsewhere in the body.
Most importantly for the sake of this post, there is the process of organ-specific metastasis. Certain types of cancers seem to have preferences for certain other organs to the exclusion of organs that remain even in close proximity to where the cancer originated (e.g., prostate cancer which often metastasizes to bone.)
Some other close assosciations include colorectal cancer which commonly metastasizes to the liver and lungs. Lung cancer, itself, which frequently metastasizes to the brain, bone, liver, and adrenal glands. Breast cancer commonly metastasize to the bone, lung, liver, and brain. So while cancer cells wind up in every nook and cranny of the body, they only “sprout” in a few places and that to a statistically significant degree.
Seed and soil
This same propensity was noticed by an English oncologist named Stephen Paget in 1889.
This same propensity was noticed by an English oncologist named Stephen Paget in 1889. Paget’s observation holds true even today. But why? The answer is that several factors account for this. One is something called the microenvironment capability.
I remember, as a boy, having a wildflower garden. I would go out into the forest and carefully dig up foxglove, ferns, and bog onions, only to replant them in my garden. One of my favorite plants was the white, waxy Indian Pipes. I could never get them to thrive because I could not faithfully create the microenvironment they needed. So it is with cancer. However, once again using an example from the plant kingdom, let me tell you a story that was positively heartbreaking to me.
I had a gorgeous dendrobium hanging in my shower once, like the one on the right, except mine had about nine canes with flowers on them. I kept it hanging on the showerhead. It was easily a $175–$250 plant. Once or twice a day, I would carefully and lovingly mist it with the sort of plastic spray bottle you might use when ironing. We had several of these misters around the house for different purposes, and one day I accidentally picked up one that had detergent in it. Within minutes of spraying the plant, I realized my error and tried frantically to wash it out of the plant and the fern slab it was rooted on, but I could not, and the plant died soon after. What I had done was manipulate the microenvironment that the plant depended on, and now it could not support the plant any longer.
“When a plant goes to seed, its seeds are carried in all directions; but they can only live and grow if they fall on congenial soil. While many researchers have been studying ‘the seeds’, the properties of ‘the soils’ may reveal valuable insights into the metastatic peculiarities of cancer cases.”
Stephen Paget – 1889
Just as plants need certain things from their micro-environment to grow, so it is with cancer. Cancer needs oxygen and nutrients just as plants do. To deliver the oxygen and nutrients, it must form new blood vessels as it grows, and this process is called angiogenesis. Angiogenesis requires certain proteins, such as vascular endothelial growth factor (VEGF), to accomplish its task.
Cancer prefers a microenvironment that provides a minimum degree of immunosuppression. This assists cancer cells in evading T cells, sentinel molecules, and oncolytic viruses. Microenvironments that are prone to inflammation are also preferred by tumors because the inflammation destabilizes normal cellular development, causing further mutations among healthy cells. I looked up those organs in the human body that are most susceptible to
inflammation and here is what I found. The number in parenthesis is how cancer of that organ ranks in the frequenvy of cancer worldwide:
Colon (3); Liver (6); Lungs (2); Breast (1) and Bladder (10)
For a number of reasons, not every oncologist is comfortable telling a patient that they have been ‘cured’ of cancer. Even my oncologist chose her words carefully when speaking to me about my bladder cancer. Five years of being cancer-free is an important milestone even today, but nothing is guaranteed.
Those cancers with which medicine has had the most success during the past decade include childhood cancers, thyroid, prostate, breast, and skin cancers. However, many variables impact success rates, including early detection, how the patient tolerates the procedures, and the comorbidities or other medical issues the patient must deal with.
In the future, advancements might be more forthcoming thanks to artificial intelligence and the rise of ‘deep learning’ (a.k.a. ‘machine learning’ or ‘black box learning’). This is a type of learning that is currently beyond human ability to explain or even understand, and it will continue to develop very rapidly. But imagine your doctor in the future prescribing you a pill for increased fertility or longer life. You ask what it is, and he doesn’t know. Nor can he explain how it works or what, if any, side effects you might encounter in the future. Conspiracy theorists would have a field day with that! As you may have noticed on your portal while reviewing your lab reports, doctors are also already using AI to assist or double-check your diagnosis and plan of care. At the moment, human decision-making is the final word, but will it be tomorrow? Each month, certainly several thousand Advanced Driver-Assistance Systems (ADAS) Level II cars are sold in the U.S. Level II cars are cars and trucks that stay in their lane and provide adaptive cruise control and braking. In theory, you could access an interstate highway and watch a movie on your phone, though I’m not sure Detroit would recommend that just yet. But we’ve seen the commercials with people not holding onto the steering wheel or a car that can parallel park by itself.
Whatever the future may hold for cancer, Paget’s seed and soil hypothesis shows the continuing value of good empirical observation and thinking. His contribution to oncology might seem trivial, but it is another piece in the tile nonetheless.
