Tag Archives: research

The Gene – An Intimate History (2/2)

This post follows on the heels of an earlier post this morning. As noted at the end of that post, about half of the sticky tabs I stuck throughout the book deal with a particular interest of mine and that’s what this post covers. What we consider as normal and not normal in terms of our physical, biological, and cognitive lives is determined in large part by how we choose to frame the definitions. 

As the 1800s was turning into the 1900s, the English doctor Archibald Garrod “had conceptually visualized a human gene and explained human variation as ‘chemical diversities’ encoded by units of inheritance. Genes make us human, Garrod had reasoned. And mutations make us different.” [bold face my addition] Garrod’s work set off “a systematic effort to create a catalog of genetic diseases in humans” and, oh my, there is an astonishing array of such diseases. Penetrance refers to the fact that “even if a mutation was present in the genome” of a person, “its capacity to penetrate into a physical or morphological feature was not always complete.” 

I am intrigued by Mukherjee’s further elaboration on these ideas as he takes us through a growing definition of disease.

The definition of disease rests, rather, on the specific disabilities caused by an incongruity between an individual’s genetic endowment and his or her current environment–between a mutation, the circumstances of a person’s existence, and his or her goals for survival or success. It is not mutation that ultimately causes disease, but mismatch. (p 264)

Even the nature of the “mismatch” is mutable: since the environment is constantly subject to change, the definition of disease has to change with it.”

…the lack of fitness–illness, in colloquial terms–was defined by the relative mismatch between an organism and environment. (p 265)

Over and over I was struck by the normalcy of differentiation among humans. It turns out that “facial features and heights are shared because genetic variations are shared among individuals,” meaning within families. Stop for a moment to consider what humanity would be like if we all looked the same with the same physical traits. How would we know who was who? And what traits would be the ones that we all had? Surely there is already a sci fi book with such a pretense. (If you know of one, please list it in a comment so I can borrow a copy from the library. Thanks!)

The natural segue is to move from pondering physical differences to intellectual differences and the influence of environment. More vocabulary words emerge from this discussion: heritable, which is a trait influenced by genes, and inheritable, which is a trait that is handed down intact from one generation to the next. (p 346) 

Using the example of growing a tall and short plant in various conditions (insufficient nourishment and appropriate nourishment), both plants grow short without the necessary nutrients, while both plants grow to their natural height with adequate nourishment, meaning the short plant grows to a short height and the tall plant grows to its tall height. Mukherjee states that

Whether genes or environment–nature or nurture– dominates in influence depends on context. When environments are constraining, they exert a disproportionate influence. When the constraints are removed, genes become ascendant. (p 347)

This is an important idea to him, and he asterisks it to a footnote on the page: There can hardly be a more cogent genetic argument for equality. It is impossible to ascertain any human’s genetic potential without first equalizing environments. [italics my addition]

There is much food for thought in this book. It is filled with a history of the discovery and science of genes, diving deep into DNA and spiraling back out to try to discern what it means to be human. I am very much in synch with Mukherjee’s thoughts about equalizing environments and think about this in the context of 38 years of teaching, 36 years of parenting, and over 60 years of living in a world consisting of beautifully diverse humans!

I leave with this image of the circular flow (p 410) of biological information, the final flow that began as a few statements many pages earlier in the text (and was noted in my previous post).circular flow

 

The Gene – An Intimate History (1/2)

In January I finished reading and wrote about The Emperor of All Maladies by Siddhartha Mukherjee. I was bemused that the history of cancer could be so captivating, all due to Mukherjee’s story telling prowess and facility with language. I immediately wanted to read more by him, and last night completed The Gene – An Intimate History.

Reading this book was no small feat! Night reading was difficult as my mind tended to wander or my eyes would droop into tiredness. I had no choice but to make this purely a the genedaytime read, meaning it took awhile to make my way through the 495 pages of text. Mukherjee’s writing sparked many questions and points of interest, as the sticky tabs attest. At one point I grabbed the nearest piece of paper, a page from the Sunday Times with sufficient white space for me to jot down my thoughts after reading pages 274-275, which is one of several times that eugenics and newgenics are discussed.

My response whilst reading those pages: If we are all alike we lose the beauty of our unique human differences because often a disease in one area yields a strength in another. That variety of strengths is what creates the range of thoughts, actions, and ideas without which we become more mono-thinking, mono-acting; we give up potential creative approaches and solutions to obstacles that life presents. “Uber-normalcy” yields inability to sustain life when, as will happen, an abnormality occurs.

Turns out, Mukherjee feels similarly. As he went on to state on the next page, “What if ‘disease-causing’ gene variants were also genius enabling?” To a certain degree, this theme percolates throughout the book as scientists uncover the foundations of genes, heredity, DNA and their inner related worlds, and discover (an ongoing process) ways of meddling in that soup. To be sure, sometimes the meddling is phenomenally beneficial, such as highly targeted approaches to cancer care. But the ability to meddle with our humanity opens up numerous safety, philosophical and ethical questions to which there are no easy or quick answers. Taken as a whole, this is a book about science, philosophy, ethics, social science, history, medicine, disease, and people.

I have gotten ahead of myself! Let’s back up to page 61, where I chuckled at chicken…was merely an egg’s way of making a better egg. This was the conclusion of Hugo de Vries, a Dutch botanist turned geneticist. de Vries built upon the work of Mendel and is credited with using the word mutants (change) to describe variations in plant life. From there he postulated that “these mutants had to be the missing pieces in Darwin’s puzzle.” And from there it became apparent that “natural selection was not operating on organisms but on their units of heredity.” Hence the italicized quote at the start of this paragraph.

Parts of this book were like biology and vocabulary lessons. (I was once exposed to some of this in high school.) The interplay of natural selection and evolution as they relate to genetics results in the words genotype, “an organism’s composition…[referring] to one gene, a configuration of genes, or even an entire genome” and phenotype, “an organism’s physical or biological attributes and characteristics–the color of an eye, the shape of a wing, or resistance to hot or cold temperatures.”

Along the lines of more basic biology and chemistry, how often do any of us stop to remember that sugars provide energy, fats store the energy, and proteins enable the chemical reactions that manage the process.

With the contemplation of the interplay of nature (genes) and nurture (environment), this led to some of the early stepping stones delineated by Mukherjee (p 107).

  • a genotype determines a phenotype
  • genotype + environment = phenotype
  • genotype + environment + triggers chance = phenotype

Slight digression – as a yoga teacher who has been known to say “let your breath be your guide” and “move with your breath,” I enjoyed the visual that came from an early chapter about the “gene molecule.” Mukherjee writes “Cells depend on chemical reactions to live: during respiration, for instance, sugar combines chemically with oxygen to make carbon dioxide and energy. None of these reactions occurs spontaneously (if they did, our bodies would be constantly ablaze with the smell of flambé sugar).” 

As the story of the gene unfolds, Mukherjee paints a picture that perfectly clarified for me the process of trying to understand DNA. He explains that

Chemists generally piece together the structure of a molecule by breaking the molecule down into smaller and smaller parts, like puzzle pieces, and then assembling the structure from the constituents. But DNA, broken into pieces, degenerates into a garble of four bases–A, D, G, and T. You cannot read a book by dissolving all of its words into alphabets. With DNA, as with words, the sequence carries the meaning. Dissolve DNA into its constituent bases, and it turns into a primordial four-letter alphabet soup. (p 216)

This post covered a little less than half of the sticky tabs stuck throughout the book as I marked pages to return for further thought. As most of the remaining tabs deal with a particular interest of mine, I will save them for a second post.

The Emperor of All Maladies: A Biography of Cancer

I recently completed the reading of this almost 500 page book. Reading about cancer might not be your idea of a “good read” but Siddhartha Mukherjee is a natural story teller and a doctor, and he tells the story of cancer with depth, discernment and loving kindness. (My Goodreads review of the book is here.)

I was intrigued by the discoveries of what cancer is, particularly that its possibility exists within each and every one of us. I don’t want to forget the explanation of how cancer gets turned on, hence this post.

As best I understand the explanation of genetics, each human cell contains two prominent genes – oncogenes and tumor suppressor genes. Oncogenes help cells grow and replicate; tumor suppressor genes inhibit cell growth. Mukherjee likens these two types of genes to putting your foot on a gas pedal (cell growth) and putting your foot on the brake (tumor suppressor genes.) When both types of genes are properly doing their job, all is well.

It is when a mutation occurs to a gene that the balance is thrown out of whack. Imagine a mutated oncogene, the gene that helps cells to grow; it would be as if the gas pedal was stuck in the down position, allowing cells to replicate with abandon. Imagine a mutated tumor suppressor gene, the gene that inhibits cell growth; it would be as if the brake was unable to be depressed, thus removing the function in the gene that stops the replicating of genes. As Mukherjee further describes the history of the discovery of how cancer comes to life he discusses specific proteins.

Genes encode proteins, and proteins often work like minuscule molecular switches, activating yet other proteins and inactivating others, turning molecular switches “on” and “off” inside a cell. … Proto-Oncogenes and tumor suppressor genes, cancer biologists discovered, sit at the hub of such signaling pathways.

Cancer, in short, was not merely genetic in its origin; it was genetic in its entirety. Abnormal genes governed all aspects of cancer’s behavior. Cascades of aberrant signals, originating in mutant genes, fanned out within the cancer cell, promoting survival, accelerating growth, enabling mobility, recruiting blood vessels, enhancing nourishment, drawing oxygen–sustaining cancer’s life.

These gene cascades, notably, were perversions of signaling pathways used by the body under normal circumstances. … Down to their innate molecular core, cancer cells are hyperactive, survival-endowed, scrappy, fecund, inventive copies of ourselves. (p 387-88)

In case you are wondering why my interest in what cancer is, I do not have a morbid curiosity. Rather, in 1998 I was diagnosed (thanks to mammography) with Stage 1 breast cancer, and treated via lumpectomy, radiation and tamoxifen. Among other things, this has made me a big proponent of mammograms and a huge fan of proactive, preventive care. I had my annual gynecological visit just a week prior to getting the mammogram, and a physical breast exam did not uncover any malady, precisely because the tumor was incredibly small. While cancer can be slow growing, it can also be fast growing, and my next mammogram would not have been for another year.

I conclude with a final quote from the last page of the book.

…to keep pace with this malady, you needed to keep inventing and reinventing, learning and unlearning strategies. (p 470)

While some cancers can be prevented (remove carcinogens in the environment such as asbestos and cigarettes), and others can be mitigated via treatment (surgery, transplants, medications), there are still others that are elusive and obstinate. Coupling the therapeutics of caring for someone with cancer, with all the myriad and sometimes debilitating approaches, and the study of cancer is insured a future history. Perhaps technology will help pave the way for deeper understanding of how our very human selves function, in turn leading to more humane approaches to care and treatment.

WHO Report on the Power of the Arts

I have posted a bit about the power of dance and, in particular, about Dance for Parkinson’s (here and here). After taking trainings with Dance for PD I became a subscriber to their site for resources and updates. It was a recent email that brought to my attention the World Health Organization’s (WHO) report reviewing “the evidence on the role of the arts in improving health and well-being.”

A few sections stood out for me – the general overview of the benefits of the arts, in particular dance and music, and the sections specific to Parkinson’s and Alzheimer’s.

GENERAL BENEFITS

The report organized the benefits under two categories: Prevention and Promotion, and Management and Treatment.

Within prevention and promotion, findings showed how the arts can:

  • affect the social determinants of health
  • support child development
  • encourage health-promoting behaviours
  • help to prevent ill health
  • support caregiving

Within management and treatment, findings showed how the arts can:

  • help people experiencing mental illness;
  • support care for people with acute conditions;
  • help to support people with neurodevelopment disorders;
  • assist with the management of noncommunicable diseases; and
  • support end-of-life care.

While the report focused on a wide range of arts, my specific interests are on the performing arts of dance, music and singing. In the report several case studies are mentioned, including Systema Europe and Dance for PD programs worldwide.

The section on Cognitive decline mentions playing a musical instrument has been found to improve or preserve…general cognition, processing speed and memory…. and dance has been linked across the lifespan with better learning and memory. Dance has  been shown to…support functional improvements in balance and attention. 

A later section in the report discusses the benefits of music to help the development of new neural pathways…and to enhance structural neuroplasticity for people who have had a stroke, as well as enhancing mental health and well-being. In the same section on neurodevelopment and neurological disorders the report details the benefits of dance to improve the motor ability of people living with Parkinson’s. Just as meaningful as the physical and cognitive benefits is the impact on participating in a Dance for PD program: …dance studies involving people with PD have also typically shown high compliance rates, low dropout and continued activity beyond the study period.

I was not surprised to see a section about how the arts can positively impact caregiving across a wide range of areas including empathy, communication, understanding, clinical skills, personal skills, and personal mental health. Music has been found to improve mood and reduce stress while working, as well as improving levels of concentration, efficiency, enthusiasm and ordered working.

If you or someone you know is dealing with any number of health related issues, there is a good chance that some form of participating in the arts can prove beneficial. To that end, I urge you to peruse the WHO report to find those sections that have meaning for you, and then jump in to find an approach or program local to you or the person for whom you are caring.