{"id":916,"date":"2022-05-11T14:01:00","date_gmt":"2022-05-11T14:01:00","guid":{"rendered":"https:\/\/darylilbury.com\/?p=916"},"modified":"2022-08-13T14:10:16","modified_gmt":"2022-08-13T14:10:16","slug":"genome-architecture-theory-shakes-up-cancer-research","status":"publish","type":"post","link":"https:\/\/darylilbury.com\/?p=916","title":{"rendered":"Genome Architecture Theory shakes up cancer research"},"content":{"rendered":"\n

It\u2019s an inconvenient truth that after 50 years of concerted research and untold billions of dollars in funding every year, a cure for cancer remains elusive. Perhaps the problem sits with the conventional view of cancer. Henry H. Heng, a professor of molecular medicine at the Wayne State School of Medicine in Detroit, Michigan, suggests we need to see the bigger picture and even rethink our understanding of evolution. His Genome Architecture Theory is telling and provocative, which is why it\u2019s attracting interest from an unlikely collaborator who sees progress in disruption.<\/strong><\/p>\n\n\n\n

It\u2019s probably true that every person who has lost a loved one to cancer has wondered at some point why there isn\u2019t a cure. It\u2019s a fair point, given the tens of thousands of scientists who have spent endless hours and billions of dollars in cancer research every year for over 50 years. The reason generally given for cancer\u2019s resolve is that there is no single \u2018cancer\u2019 and that every cancer in every patient is, to a degree, different. There is some truth to that, although there could be a simpler but more sensational reason: our fundamental understanding of cancer is wrong. If that is true, it could explain why common treatments for cancer seem to miss the mark.<\/p>\n\n\n\n

One cancer researcher supports such reasoning. Dr Henry H. Heng is a professor of molecular medicine, genetics, and pathology at the Karmanos Cancer Institute at the Wayne State School of Medicine in Detroit, Michigan, in the US. His main research area is molecular cytogenetics and cytogenomics \u2013 the relationship between chromosomes, gene expressions and cell function\/behaviour \u2013 in somatic cancer cells. Over decades of research, Heng has noticed that when cells become \u2018cancerous\u2019 or tumour cells undergo significant phase transitions \u2013 say from being localised to metastasising or from drug sensitive to drug resistant \u2013 most of them display dramatic changes in their karyotypes \u2013 the number of chromosomes and the genes\u2019 ordering of the cell\u2019s chromosomes \u2013 to the point that they are fundamentally different cellular organisms. Moreover, he illustrates how these significant changes occur when the cells are exposed to high stress during a crisis \u2013 such as an environmental event or medical treatment \u2013 resulting in a chaotic \u2018rewiring\u2019 of the entire genome. According to his new theory, the genome is not simply a \u2018bag of genes\u2019 but represents higher-order system information that organises gene interactions. Thus, chromosomal changes are actually the key drivers for cancer evolution.<\/p>\n\n\n\n

This theory clashes significantly with the standard understanding that cancer develops when a few common, specific gene mutations accumulate in the body, triggering the production of aberrant cells. Importantly, whether benign or malignant, these cells are considered the host\u2019s cells, just dysfunctional, displaying out-of-control growth. Therefore, treatment should involve targeting these bad gene mutations or maximally killing as many cancer cells as possible, battering the aberrant cells into submission. Heng disagrees, saying cancerous cells are so different in their genome architectures they\u2019re akin to a different cellular species in the host. Subsequently, Heng believes \u2018standard\u2019 gene mutation-based cancer theory demands a complete rethink, as do some treatments it supports, such as chemotherapy that can induce drug resistance and make cancer more deadly. Suffice to say, this rankles the pantheon of cancer researchers who reject non-conformism and the idea they could be wrong. But here\u2019s the rub: Heng has history, science, and precedent on his side.<\/p>\n\n\n\n

\"\"
Human Cancer Cell Image: Luis Molina\/Getty Images<\/figcaption><\/figure><\/div>\n\n\n\n

The mavericks<\/h3>\n\n\n\n

Science doesn\u2019t know everything; if it did, it would stop. The gaps in our scientific knowledge close at a seemingly glacial pace, primarily due to the immeasurable scope of the study \u2013 the natural world in all its vastness and complexity \u2013 and the speed at which research takes place. Traditionally, the picture we develop of our natural world comes through the meticulous, step-by-step joining of microscopic pieces of insight derived from growing data \u2013 like parts of a puzzle \u2013 around an established framework of thinking: a theory. But every now and then, a maverick \u2013 or non-conformist \u2013 scientist with a critical eye comes along and suggests the framework is wrong, and we need to rethink our approach.<\/p>\n\n\n\n

Such scientists are essential to the very health of science \u2013 they encourage us to re-examine conventional wisdom, especially when that wisdom seems significantly flawed. The fundamental surgical process of hand scrubbing was once considered non-conformist. Einstein unwound Newton\u2019s clockwork universe where time and space were absolutes. Lynn Margulis shocked biologists in the late 1960s with her theory that vital structures within eukaryotic cells, upon which all complex life is based, came from simple bacteria swapping genetic code \u2013 an idea now considered mainstream. And for decades, the notion that bacteria caused stomach ulcers was met with scorn in scientific circles until two Australian researchers proved dramatically otherwise, earning them the Nobel Prize in Physiology or Medicine in 2005.<\/p>\n\n\n\n

Heng fits the bill of a science maverick: a senior, highly accomplished, and meticulous researcher who has, through insight, contentment in chaos, or a dissenting disposition, investigated a problem from a different angle. Yet his idea is hardly surprising; it\u2019s evidenced in evolution. <\/p>\n\n\n\n

The alien in our body<\/h3>\n\n\n\n

Darwin\u2019s theory of evolution was based on gradual, minuscule genetic changes over long periods of time. This \u2018micro-evolution\u2019 was determined by the successful genetic traits of successive generations of individuals within a species adapting to their surroundings. However, this doesn\u2019t explain fossil records that show long periods of micro-evolution stasis with occasional \u2018macro\u2019 leaps in evolution. This \u2018punctuated evolution\u2019 could only occur if there were two phases: a macro-evolution spurred by some external event that triggers a dramatic and seemingly chaotic, yet successful, rewiring of a species\u2019 genome architecture, followed by micro-evolution \u2013 the more Darwinian genetic \u2018fine-tuning\u2019.<\/p>\n\n\n\n

For Heng, just as this genome chaos creates species diversity, so too does it explain the disordered cellular variegation we call cancer. Speciation and cancer metastasis are both forms of chaos-triggered macro-evolution; ergo, a clump of cancerous cells in a person\u2019s body is like a new species, as are the evolutionary \u2018leaps\u2019 of cancer\u2019s emergence. Such an approach to cancer may sound far-fetched, but, as such, it does have evidence in the fossil record. That doesn\u2019t mean science is willing, just yet, to accept Genome Architecture Theory.<\/p>\n\n\n\n

However, some believe it\u2019s time for cancer research to have its own evolutionary leap. For that, it needs an injection of energy, a spark to initiate a chaotic burst \u2013 a radical rewiring of cancer research\u2019s architecture. Given Heng\u2019s maverick status, it\u2019s doubtful it\u2019ll come from academia. Luckily, he\u2019s been dealt a rather fortunate hand.<\/p>\n\n\n\n

\"\"
Image: National Cancer Institute\/Unsplash<\/figcaption><\/figure><\/div>\n\n\n\n

The power of disruption<\/h3>\n\n\n\n

Rafe Furst is a former World Series of Poker champion with a master\u2019s degree in computer science and artificial intelligence from Stanford, who turned his deft skills towards tech entrepreneurship and investing in big ideas and maverick individuals. He has also raised considerable money for cancer research and was elected to the board of the Prevent Cancer Foundation. His and Heng\u2019s paths crossed at a conference where Heng presented his theory of genome chaos. Furst was fascinated with the idea and became frustrated that it wasn\u2019t gaining traction with other researchers. His high-stakes competitive streak kicked in, and he decided to challenge academic inertia.<\/p>\n\n\n\n

In a recent submission to the journal Progress in Biophysics and Molecular Biology,<\/em> titled \u2018The Importance of Henry H. Heng\u2019s Genome Architecture Theory\u2019, Furst presents Heng\u2019s key arguments in simple language (\u201cInheritance is not precise, it\u2019s fuzzy\u201d) and sound logic, stripped of confusing academic trivialities. He employs unpretentious analogies and provocative wording, breaking down the intricacies of Heng\u2019s theory into 11 basic points. For example, he explains that the whole genome (not the gene) is the primary unit of heritable information upon which evolution by natural selection works. <\/p>\n\n\n\n

In effect, Furst pushes Heng\u2019s Genome Architecture Theory into the open, celebrating its maverick nature and scientific rigour. His message has all the confidence of a master poker player: it is time for Heng and other aligned mavericks to go all-in \u2014 collectively \u2014 and disrupt the evolutionary establishment, colloquially known as Modern Synthesis and neo-Darwinism.<\/p>\n\n\n\n

Rattling cages<\/h3>\n\n\n\n

Science is watching what will happen now, probably intrigued at Heng and Furst\u2019s alliance. At first glance, the two make an unlikely pair: the quiet, bookish, seasoned academic scientist and the self-assured entrepreneur and impact investor. But they are bonded by an unwillingness to bow to convention in the quest to revolutionise cancer research. They\u2019re also not holding back. Genome Architecture Theory is bigger than cancer research \u2013 it\u2019s part of a more significant shake-up of evolutionary theory. And Heng and Furst are not alone in their efforts, as the movement has been pushed forward recently by  some big names in biology, including James Shapiro and Denis Noble<\/a> as well as another entrepreneur-turned-evolution-maverick, Perry Marshall<\/a>. Cages are being rattled, and scientific egos look likely to fall.<\/p>\n\n\n\n

Heng has spent decades testing, retesting, and fine-tuning his Genome Architecture Theory, more importantly, arguing for its place in rethinking our understanding of cancer. Two things to this point are true: while scientific knowledge is sometimes upended for the good by non-conformist thinking, the inertia of scientific conformity is largely uninviting to those who challenge the status quo; and, after 50 years of conformist thinking around cancer research, treatment has changed very little, and a cure seems still far away. Heng has found a valuable ally in Furst and the other mavericks. This combination of scientific gravitas and entrepreneurial disruption may now be pushing the field closer to understanding the true nature of cancer, which is a prerequisite for more successful treatments and ultimately (if possible) a cure.  <\/p>\n\n\n\n

Originally published in Research Features on May 11, 2022<\/a>.<\/p>\n\n\n\n

Photo by National Cancer Institute<\/a> on Unsplash<\/a>.<\/p>\n\n\n\n

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