Unintelligent Designer News - An Enzyme Which Protects Us Against Viruses Also Causes Cancers. Is this Malevolence or Incompetence?

Enzyme That Protects Against Viruses Could Fuel Cancer Evolution | Newsroom | Weill Cornell Medicine

A three-dimensional image of a cancer cell's nucleus obtained by Dr. Faltas and his team shows the APOBEC3G protein (green) inside the nucleus (blue).

In a stunning example of unintelligent design, an enzyme that Creationists have to believe was designed by their putative omniscient designer god to protect us from the viruses it designs to make us sick, also causes cancers. Whether this is evidence of malevolence or incompetence is difficult to say, if you believe the Creationist claims. What it can't in all honesty be presented as is evidence of supreme intelligence and omnibenevolence.

Fortunately, people who understand evolutionary biology don't need to concern themselves with those sorts of questions because they know a mindless, utilitarian natural process like evolution is not a sentient entity and therefore has no intent. Arms races such as that between our immune system and viruses is entirely predictable, as is the example of trade-off between protecting against viral infection and causing cancer. The only test of effectiveness is in the number of descendants that survive to reproduce.

The role of the enzyme, called APOBEC3G, which protects human cells against retroviral attack, in promoting cancer was discovered by a team lead by researchers at Weill Cornell Medicine who used a preclinical model of bladder cancer to investigate the role of the enzyme in promoting the disease and found that it significantly increased the number of mutations in tumour cells, boosting the genetic diversity of bladder tumours, making it harder to treat and hastening mortality.. They have published their findings in the journal Cancer Research, sadly behind a paywall.

The Weill Cornell Medicine news release gives details:

Our findings suggest that APOBEC3G is a big contributor to bladder cancer evolution and should be considered as a target for future treatment strategies.

These findings will inform future efforts to restrict or steer tumor evolution by targeting APOBEC3 enzymes with drugs.

Dr.Bishoy M. Faltas, corresponding author.
Assistant professor of medicine
Division of Hematology and Medical Oncology and of cell and developmental biology
Weill Cornell Medicine, New York, USA.

The APOBEC3 family of enzymes is capable of mutating RNA or DNA—by chemically modifying a cytosine nucleotide (letter “C” in the genetic code). This can result in an erroneous nucleotide at that position. The normal roles of these enzymes, including APOBEC3G, are to fight retroviruses like HIV—they attempt to hobble viral replication by mutating the cytosines in the viral genome.

The inherent hazardousness of these enzymes suggests that mechanisms must be in place to prevent them from harming cellular DNA. However, starting about a decade ago, researchers using new DNA-sequencing techniques began to find extensive APOBEC3-type mutations in cellular DNA in the context of cancer. In a 2016 study of human bladder tumor samples, Dr. Bishoy M. Faltas, corresponding author, who is also director of bladder cancer research at the Englander Institute for Precision Medicine and a member of the Sandra and Edward Meyer Cancer Center, found that a high proportion of the mutations in these tumors were APOBEC3-related—and that these mutations appeared to have a role in helping tumors evade the effects of chemotherapy.

Such findings point to the possibility that cancers generally harness APOBEC3s to mutate their genomes. This could help them not only acquire all the mutations needed for cancerous growth but also boost their ability to diversify and “evolve” thereafter—enabling further growth and spread despite immune defenses, drug treatments, and other adverse factors.

In the new study, Dr. Faltas and his team, including first author Dr. Weisi Liu, a postdoctoral research associate, addressed the specific role of APOBEC3G in bladder cancer with direct cause-and-effect experiments.

APOBEC3G is a human enzyme not found in mice, so the team knocked out the gene for the sole APOBEC3-type enzyme in mice, replacing it with the gene for human APOBEC3G. The researchers observed that when these APOBEC3G mice were exposed to a bladder cancer-promoting chemical that mimics the carcinogens in cigarette smoke, they became much more likely to develop this form of cancer (76% developed cancer) compared with mice whose APOBEC gene was knocked out and not replaced (53% developed cancer). Moreover, during a 30-week observation period, all the knockout-only mice survived, whereas nearly a third of the APOBEC3G mice succumbed to cancer.

We saw a distinct mutational signature caused by APOBEC3G in these tumors that is different from signatures caused by other members of the APOBEC3 family.

Dr. Liu, first author
Weill Cornell Medicine, New York, USA.

To their surprise, the researchers found that APOBEC3G in the mouse cells was present in the nucleus, where cellular DNA is kept using an ‘optical sectioning’ microscopy technique. Previously, this protein had been thought to reside only outside the nucleus. They also found that the bladder tumors of the APOBEC3G mice had about twice the number of mutations compared to the tumors in knockout-only mice.

Identifying the specific mutational signature of APOBEC3G and mapping it in the tumor genomes, the team found ample evidence that the enzyme had caused a greater mutational burden and genomic diversity in the tumors, likely accounting for the greater malignancy and mortality in the APOBEC3G mice.

Lastly, the researchers looked for APOBEC3G’s mutational signature in a widely used human tumor DNA database, The Cancer Genome Atlas, and found that these mutations appear to be common in bladder cancers and are linked to worse outcomes.

The role of the enzyme, called APOBEC3G, ehich protects human cells against viral attack, in promoting cancer was discovered by a team lead by researchers at at Weill Cornell Medicine wwho used a preclinical model of bladder cancer to investigate the role of the enzyme in promoting the disease and found that it significantly increased the number of mutations in tumor cells, boosting the genetic diversity of bladder tumors, making it harder to treat and hastening mortality.. They have published their findings in the journal , sadly behind a paywall.
The authors give more details in the abstract to their paper in Cancer Research:

Abstract

Mutagenic processes leave distinct signatures in cancer genomes. The mutational signatures attributed to APOBEC3 cytidine deaminases are pervasive in human cancers. However, data linking individual APOBEC3 proteins to cancer mutagenesis in vivo are limited. Here, we showed that transgenic expression of human APOBEC3G promotes mutagenesis, genomic instability, and kataegis, leading to shorter survival in a murine bladder cancer model. Acting as mutagenic fuel, APOBEC3G increased the clonal diversity of bladder cancer, driving divergent cancer evolution. Characterization of the single base substitution signature induced by APOBEC3G in vivo established the induction of a mutational signature distinct from those caused by APOBEC3A and APOBEC3B. Analysis of thousands of human cancers revealed the contribution of APOBEC3G to the mutational profiles of multiple cancer types, including bladder cancer. Overall, this study dissects the mutagenic impact of APOBEC3G on the bladder cancer genome, identifying it contributes to genomic instability, tumor mutational burden, copy-number loss events, and clonal diversity.

Liu, Weisi; Newhall, Kevin P.; Khani, Francesca; Barlow, LaMont; Nguyen, Duy; Gu, Lilly; Eng, Ken; Bhinder, Bhavneet; Uppal, Manik; Récapet, Charlotte; Sboner, Andrea; Ross, Susan R.; Elemento, Olivier; Chelico, Linda; Faltas, Bishoy M.
The cytidine deaminase APOBEC3G contributes to cancer mutagenesis and clonal evolution in bladder cancer
Cancer Research (2022); CAN-22-2912, DOI: 10.1158/0008-5472.CAN-22-2912

© 2022 the American Association for Cancer Research.
Reprinted under the terms of s60 of the Copyright, Designs and Patents Act 1988.

Let's just recap, for the benefit of Creationists who need to understand the god they worship and which they seek to fool others into worshipping too:

1. The intelligent designer designed viruses, knowing that they would make us sick.
2. It then designed our immune system to protect us from the viruses it designed to make us sick.
3. One of the enzymes in this system is APOBEC3G, which attacks retroviruses by causing the cytosine in the viral DNA, embedded in the human genome, to mutate.
4. The same enzyme also causes the DNA in cancer cell to mutate, so mutations can evade the treatments medical science has made and making them better at making us sick and killing us.

So, any designer of this system either didn't understand the consequences of its design, when it designed viruses, when it designed the APOBEC3G enzyme or when it designed cancer to mutate and evade the treatments medical science has invented, so can't be regarded as intelligent; or it did fully understand the consequences of it designs, so can only be regarded as malevolent.

What no rational person can argue is that the putative designer of this system bears any resemblance to the supremely intelligent, all-loving god Creationists would have their dupes believe.

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Thank you for sharing!

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