Telomeres shown as white caps on the ends of the chromosome arms.
Examples from nature in which, if creationist arguments for the existence of an intelligent designer are applied consistently, that designer can only be regarded as a malevolent entity intent on increasing suffering in the world, continue to accumulate. And the more examples there are, the more creationists need to ignore their own arguments, abandon any pretence that creationism is a genuine alternative science, and retreat instead into the fundamentalist biblical myths of 'The Fall' and 'Original Sin'. The evidence remains the same; only the interpretation is twisted to preserve the preferred narrative.
The latest such example concerns the genetics behind one of malignant melanoma's most dangerous properties: its ability to evade the normal cellular limit on repeated division. This had long been a missing piece in understanding how melanoma cells avoid the ordinary route to cellular senescence and continue to proliferate. Like Michael J. Behe's and William A. Dembski's supposed 'evidence' for intelligent design, it depends on a set of interacting components being in place and on genetic changes producing just the right molecular effect — precisely the kind of arrangement the Discovery Institute insists cannot arise by natural processes because, in its caricature of biology, evolution is merely 'random chance'. That claim, of course, ignores the elementary biological fact that natural selection makes evolution very much a non-random process.
The discovery, published in Science in November 2022 by Pattra Chun-on, Jonathan K. Alder and colleagues, concerns telomeres — the protective caps at the ends of chromosomes. In most normal somatic cells, telomeres gradually shorten with repeated cell division until the cell can no longer divide. This is one of the body's safeguards against uncontrolled proliferation. Cancer cells, however, often find ways to bypass this limit, and melanoma has long been known for having unusually long telomeres, even compared with many other cancers. What had not been fully understood was how melanoma achieved this.
The answer involves telomerase, the enzyme complex that lengthens telomeres. In most normal adult cells, telomerase activity is switched off or kept very low. Many melanomas carry mutations in the promoter region of TERT, the gene that encodes the catalytic component of telomerase, and these mutations increase telomerase activity. But that turned out to be only part of the story. When researchers introduced TERT promoter mutations into melanocytes, they did not reproduce the exceptionally long telomeres seen in melanoma tumours.
The missing component was TPP1, a member of the shelterin complex that helps regulate telomeres. The researchers found that mutations in the promoter region of ACD, the gene that encodes TPP1, can increase TPP1 production. When these TPP1-promoter mutations occur together with TERT promoter mutations, the two changes cooperate to produce the long telomeres characteristic of melanoma. In other words, melanoma's ability to evade normal cellular mortality depends on a coordinated interaction between altered telomerase activity and altered telomere regulation.
So, in intelligent-design creationist terms, we have a system requiring interacting molecular components, each specified by genetic changes in ordinary cellular genes, and each contributing to a result that benefits the cancer cell at the expense of the patient. If the same kind of molecular cooperation in a harmless or useful organism is to be paraded as evidence of design, then consistency demands the same conclusion here. Melanoma, on that argument, would be another product of the same intelligent designer — one whose ingenuity is directed towards helping cancer cells escape the body's normal restraints.
Of course, the scientifically honest conclusion is not that melanoma was designed, malevolently or otherwise. It is that cancer exploits the same evolved molecular machinery that normal cells use, and that mutations filtered by selection within the tumour can favour cells that divide faster, survive longer and outcompete their neighbours. The creationist problem is that the very mechanisms they claim as evidence for their designer are just as plainly at work in disease, parasitism and suffering.
Telomeres, Telomerase and Cellular Immortality. Telomeres are repeated DNA sequences at the ends of chromosomes. They act rather like the protective plastic tips on shoelaces, preventing chromosome ends from fraying, fusing with other chromosomes, or being mistaken by the cell as broken DNA.The paper in Science was accompanied by an item in the University of Pittsburgh's online magazine, Pittwire, by Hayley Rein:
Every time most normal body cells divide, their telomeres become a little shorter. Eventually, they become too short for the cell to continue dividing safely. At that point, the cell normally enters a state called senescence, in which it remains alive but no longer divides, or it may undergo programmed cell death. This is one of the body's natural defences against uncontrolled cell growth.
Telomerase is an enzyme complex that can lengthen telomeres. It is active in cells that genuinely need long-term division potential, such as stem cells, germ-line cells and some immune cells. In most ordinary adult body cells, however, telomerase is switched off or kept at very low levels. This helps place a limit on how many times those cells can divide.
Cancer cells often evolve ways to bypass this limit. By reactivating telomerase, or by using other mechanisms to maintain telomeres, they can avoid the normal countdown to senescence. This does not make them immortal in any supernatural sense, but it does give them one of the key properties of cancer: the ability to keep dividing when normal cells would stop.
In melanoma, researchers have found that mutations affecting telomere maintenance can cooperate. Mutations in the promoter region of TERT, the gene for the catalytic component of telomerase, can increase telomerase activity. But, in melanoma, that is not always enough on its own. Additional promoter mutations affecting ACD, the gene that encodes the telomere-binding protein TPP1, can increase TPP1 production and help telomerase act more effectively at chromosome ends.
The result is a molecular system that helps melanoma cells maintain unusually long telomeres and so continue dividing. In evolutionary terms, this is not design but selection within a tumour: any cell that acquires mutations allowing it to divide more successfully may leave more descendant cancer cells. What looks superficially like a clever solution is, in reality, the blind exploitation of ordinary cellular machinery by a population of mutated cells.
Pitt scientists discovered a key genetic step in melanoma’s race to live forever
Scientists at the University of Pittsburgh School of Medicine have discovered the missing puzzle piece in the mystery of how melanoma tumors control their mortality.
In a paper published in Science, Jonathan Alder, and his team describe how they discovered the perfect combination of genetic alterations that tumors use to promote explosive growth and prevent their own demise, a development that could change the way oncologists understand and treat melanoma.
We did something that was, in essence, obvious based on previous basic research and connected back to something that is happening in patients.
Assistant Professors Jonathan K. Alder, Senior author
Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease
Division of Pulmonary, Allergy, and Critical Care Medicine
Pittsburgh, PA, USA.
Telomeres, protective caps at the of the end of the chromosome (shown above), are required to prevent DNA from degrading. In healthy cells, telomeres become shorter with each cycle of replication until they become so short that the cell can no longer divide. Disruptions in maintenance of the length of the telomeres can lead to severe disease. Short telomere syndromes lead to premature aging and death, but extra-long telomeres are associated with cancer.
For years, scientists have observed strikingly long telomeres in melanoma tumors, especially in comparison with other cancer types.
There’s some special link between melanoma and telomere maintenance. For a melanocyte to transform into cancer, one of the biggest hurdles is to immortalize itself. Once it can do that, it’s well on its way to cancer.
Assistant Professors Jonathan K. Alder.
The telomerase protein is responsible for elongating telomeres, protecting them from damage and preventing cell death. Telomerase is inactive in most cells, but many types of cancers use mutations in the telomerase gene, TERT, that activate this protein and allow cells to continue growing. Melanoma is particularly well-known for doing just this.
About 75% of melanoma tumors contain mutations in the TERT gene that stimulate protein production and increase telomerase activity. Yet, when scientists mutated TERT in melanocytes, they weren’t able to produce the same long telomeres seen in their patient’s tumors. It turned out that TERT promoter mutations were just half of the story.
With a background in cancer biology and a new interest in telomeres, Pattra Chun-on, an internist earning her PhD in Alder’s lab, was determined to find the missing link between melanoma, TERT promoter mutations and long telomeres.
The fun part of this story is when Pattra joined my lab. She contacted me and told me that she was interested in studying cancer. I told her that I study short telomeres and not long telomeres. This went on until I realized that Pattra would never take ‘no’ for an answer.
Assistant Professors Jonathan K. Alder.
While combing through cancer mutation databases, Alder’s lab team had previously discovered a region in a telomere binding protein called TPP1, which was often mutated in melanoma tumors.
Chun-on’s determination in the lab shone when she found that the mutations in TPP1 were strikingly similar to those of TERT; they were located in the newly annotated promoter region of TPP1 and stimulated production of the protein. This was exciting to Alder because TPP1 has long been known to stimulate telomerase activity.
Biochemists more than a decade before us showed that TPP1 increases the activity of telomerase in a test tube, but we never knew that this actually happened clinically.
Assistant Professors Jonathan K. Alder.
When Chun-on – who is also part of a PhD program in the Department of Environmental and Occupational Health at Pitt’s School of Public Health – added mutated TERT and TPP1 back to cells, the two proteins synergized to create the distinctively long telomeres seen in melanoma tumors. TPP1 was the missing factor scientists had been searching for, and it was hiding in plain sight all along.
This discovery has changed the way scientists understand the onset of melanoma, but it also has the potential to improve treatment. By identifying a telomere maintenance system that is unique to cancer, scientists have a new target for treatments.
Publication:
What this research shows, yet again, is that the living world is not arranged as we would expect if it were the product of a benevolent, omnipotent intelligence designing organisms for human welfare. It is arranged exactly as we would expect if natural processes, acting without foresight or morality, can be exploited by any cell line, parasite or pathogen that gains a selective advantage from them. In this case, the beneficiaries are melanoma cells, and the cost is paid by the patient.
For intelligent-design creationists, the difficulty is obvious. The same kind of molecular coordination that they present as evidence of design when it occurs in a bacterial flagellum, an immune system or a metabolic pathway is also found in cancer. If interacting parts, genetic information and functional integration are evidence of an intelligent designer, then melanoma’s ability to evade normal cellular mortality must be credited to that designer too. To accept the argument in one case and reject it in the other is not science; it is special pleading.
The predictable escape route is to invoke 'The Fall', 'Original Sin', or some other theological device, but that merely confirms that creationism is not an alternative scientific explanation at all. It is a narrative-preservation exercise. The evidence is first declared to show design, then, when the design turns out to be malignant, wasteful or cruel, the same evidence is reinterpreted to protect the dogma from its own implications.
Science has no need of such evasions. Mutations occur; some alter gene regulation; cells that gain a reproductive advantage within a tumour population leave more descendants. That is evolution by selection, operating inside the body, with no plan, no purpose and no regard for human suffering. Melanoma does not point to a designer. It points to the blind, opportunistic and morally indifferent nature of biological processes — the very processes creationists keep pretending biology has somehow outgrown.
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