Jay Kulsh

Thank you both. @Sensei, the Wikipedia article you cited does talk about cancer when discussing Genetic disorder.

Has any oncogene (cancer causing gene) been identified whose presence always causes cancer and whose absence keeps a tissue free of cancer? (I would have preferred to post this question in some medicine category, but was not able to find a suitable category, like oncology.) Jay

Arete, you sure provide good links. It will take me a while to go through them. Thanks.

You cite "Even if the net number of deleterious mutations outnumber the beneficial, the process of selection increases the likelihood of fixation of beneficial mutations." It seems to me, this "process of selection" rationale works only for lower organisms like virus and bacteria which may multiply millions times or more in a day, and can afford to go in thousand wrong directions -- but not for higher organisms which produce a few off-springs in a year. (We might be going in circles now...)

Most mutations may be neutral, but harmful mutations must still outnumber beneficial ones, if they are truly random.

CharonY, Thanks for your valuable post. You are totally correct about how a 'beneficial' mutation in a virus would survive/thrive, even if most mutations are not 'beneficial' to its survival -- due to fast and furious way it multiplies. But what about higher organisms like mammals where only a few progenies are produced in an entire year? Since most random mutations cannot be beneficial, how are they eliminated? They may not do any immediate harm, if genetic contribution of other parent mask their effect, but sheer accumulation of them in genome would be very bad in the long run. We do not even detect a whole lot of such harmful mutations. They certainly cause some genetic diseases but these are very rare -- afflicting probably less than 1% of the population. Search on Internet for "Epigenetics Lamarck" yields two kind of scientific discussions: In the first group, Lamarck is remembered fondly while discussing epigenetics: Epigenetic Change: Lamarck, Wake Up, You're Wanted in the ... On epigenetics: we need both Darwin's and Lamarck's ... - Aeon In the other group, introduction of name of Lamarck is not welcome: Epigenetics is Normal Science, But Don't Call It Lamarckian ... (PDF) Why epigenetics is not a vindication of Lamarckism ... I obviously agree with the first group, while you favor the 2nd one. (I am not saying Epigenetics is equivalent to Lamarckism, only that it has shades of Lamarckism, and there is a lot more to come since epigenetics is its infancy.) Let us agree to disagree and I am closing this thread with you. Thanks for providing some good links.

"some sort of ability to control the novel gametic mutations it inherits or passes on." I did imply that. Is this not what epigenetics is? There are certainly some examples where genes responds to environmental stresses and those modifications gets inherited. Epigenetics is in its infancy. Till a few decades ago, ideas that are now accepted under epigenetics, were being laughed at. (Late Stephen J. Gould despised Lamarck with gusto. A day may come when Gould will be looked down upon for this and other reasons.) Just look at Covid-19 virus. Within a year -- an extremely short time on the evolutionary scale -- it has mutated so that now it is more infectious. When 'random' mutations are favorable over and over -- despite having extreme odds against such occurrences -- then those mutations cannot truly be random. We just don't yet understand the underlying mechanism of the phenomenon.

Arete, I had taken the phrase "Interactive" from the title of your own citation: "Interaction-based evolution".

Arete, Your reply seems more meaningful than others. Thanks for the link at "they aren't actually random". (Some others have simply stated that thinking of the original question is wrong, without saying a word why? I was seeking discussion, not a verdict.) Most random mutations may be neutral, but number of harmful such mutations would surely exceed beneficial ones. Let me point out a scenario when beneficial mutation would have to occur in multiple places for evolution to move forward, increasing odds against it. For example, when oceanic creatures first started moving to land. To survive on land, they had to not be able to just drag/crawl their bodies in mud or dry land, but they also had to breath oxygen directly from air -- and face direct sunlight, etc. Therefore, multiple random beneficial mutations had to occur in concert to be of any help in survival. Could a phenomenon like epigenetics have not played a role, where a mutation is not random but "effortful" or "interactive"? Thanks.

Genes can mutate in about 7 ways, namely Missense mutation Nonsense mutation Insertion Deletion Duplication Frameshift mutation Repeat expansion In each of these mutation types, there are multiple possibilities, for example a deletion can happen in any portion of the gene and it can be small or large. All in all, there are at least hundreds of thousands of ways in which an average gene (that can build protein of 200 - 300 amino acids) can mutate. Only a very few of these mutation would be beneficial while most of them will be harmful. To think that random genetic mutations kept leading to beneficial changes over hundred of millions years is like saying a person can keep winning lottery over and over, even though each time his/her odds are 1 in 100,000 or 1 in 1,000,000. Is this line of thinking wrong? Could sheer randomness have led to so many refinements to various forms of life on the planet? Thanks.

John, Thanks for pointing out similarity of GEIPE treatment to Cisplatin. GEIPE works by disabling the enzyme RnR which controls the bottleneck step in DNA replication. Cisplatin works in part by binding to DNA and inhibiting its replication. Advantages of GEIPE over Cisplatin: It is non-toxic, and therefore should have much wider applicability. (Cisplatin is primarily effective for testicular cancers.) It stops DNA replication -- only in cancerous tissues, as various experiments attest -- at more fundamental level by preventing synthesis of building blocks (4 bases) of DNA. Disadvantages of GEIPE over Cisplatin: It is non-patentable -- and thus of no interest to cancer institutions. This unique 'disadvantage' has won the day for more than 25 years. From the perspective of suffering and dying cancer patients, a way out must be found, somehow, some day.

It is interesting that you wonder about the "model of the mechanism" for the effectiveness of gentle electrotherapy to treat cancer. My contribution to this therapy is just that. It is based on quenching of free-radical at the active site of enzyme Ribonucleotide Reductase (RnR) which is bottleneck enzyme for DNA synthesis as well as cancer growth. Here is my published article on the subject: https://cancer-treatment.net/novel-cancer-therapy-1997-article.htm More information is available at the home page of the website: https://www.cancer-treatment.net which belongs to a California Non-Profit. BTW, your link to the 1985 article is certainly better than mine. Thanks.

Thanks for responding. I was a bit reluctant to provide link to the article since was not sure if I am in the right section of the forum. Here it is: https://cancer-treatment.net/Ref.7-Journal-Cancer-Research-Article-of-1985.htm What you are saying is true in general for cancer research, but not in this case. I spoke at length with the lead author of above study and he informed me that they could not get funding. Please see his letter to me: https://cancer-treatment.net/from-very-positive-cancer-therapy-study-author.htm This cancer treatment is certainly not toxic. And this treatment is just as effective in humans as in animals. Please see this scientific publication: https://cancer-treatment.net/languishing-promising-cancer-therapy-2014-article.htm

I wish to discuss a Biochemistry-Biophysics based treatment of Cancer, that has been languishing for more than 25 years because it is not patentable. A 1985 study published in the journal Cancer Research showed 98% reduction of tumors in 5 hours over 5 days of treatment? Strangely there were no follow ups. Thanks. Jay