Welcome, readers of my blog. This post you are viewing is number two-hundred in a long line of mini-essays which have appeared in this space since my first, titled The Lure of Science, in February of 2013. Writing about little things such as my reflections on life has provided me much pleasure and a satisfying outlet. While relishing small pleasures along the way, I remain forever intrigued with the BIG thoughts, the truly great accomplishments, and the monster minds which formulated them. I devote this special post, number two-hundred, to one of the great chapters in scientific history – discovering the double-helix nature of DNA.
The subject at hand is DNA, an acronym for the scientific term deoxyribonucleic acid. DNA is literally the blueprint of life – all life on this planet. What is more mysterious than life, itself? Think of DNA molecules quite literally as the repository of nature’s software program for all forms of life, the coding of which uniquely defines each and every one of us, not only as a species, but as distinct individuals. The biological hierarchy which defines us is complex; suffice it to say that DNA is the “instruction set” for our genes, those next-level entities which determine what and who we are.
I have begun reading Walter Isaacson’s newest book release titled, The Code Breaker. The story focuses on the 2020 Nobel Prize winner in biology, Jennifer Doudna, and the story of CRISPR which is an acronym for the gene editing technology which is now quite advanced – to a large extent, because of her work. To the best of my understanding (so far), the question has rapidly become not how to do this (gene editing), but should we do this. Author Isaacson does his subjects justice in his book. I say subjects, plural, because he deftly weaves Ms. Doudna’s story within a larger tapestry which includes the crucial efforts of scientific colleagues, particularly Nobel co-winner Emmanuele Charpentier. Isaacson couples all of this with a healthy dose of what Nobel-winning scientific endeavors are all about.
The scientific stakes are huge, here. So, too, is the competitive drive necessary to be first with the qualifying research and the scientific papers that justify Nobel-level consideration. This very theme, the competition for scientific immortality, has been repeated countless times throughout the history of science. Among the most reminiscent, for me, is the account by James Watson of his famous collaboration with Francis Crick to discover the structure of the DNA molecule itself. For their revelation in 1953 of the double-helix backbone structure supporting a four base-protein coding of cross-ties, these two researchers were awarded the 1962 Nobel Prize along with a third researcher, Maurice Wilkins.
James Watson’s account of DNA’s discovery appeared in his famous book, The Double Helix: A Personal Account of the Discovery of the Structure of DNA, first published in 1968. This book, with its revelation of the scientific discovery and the frank candor of its author, reads like a suspenseful, non-fiction detective story as opposed to what could have been a dry, scientific tome. In the book, Watson describes not only the science, but the competitive endeavor in which he and Crick found themselves immersed: the struggle to be first to finally decipher the biological holy grail – the structure of the DNA molecule. Linus Pauling, world-famous chemist, and Rosalind Franklin, a brilliant, pioneering female researcher are other significant players in the competitive drama and Watson devotes considerable ink to describing them and their roles in the unfolding event.
Once the double-helix nature of DNA was revealed by Watson and Crick, some important questions were resolved, specifically, how DNA can replicate itself and how male/female DNA are combined to produce those recognizable features of each that typically appear in offspring. Of course, the latest gene-editing findings by Jennifer Doudna and her fellow researchers all leverage-off the nature of the DNA molecule as first described by Watson and Crick. Enough said about the importance of Watson and Crick’s findings to the state of today’s biology!
Biological Inheritance … As We Came to Understand It
Prior to Charles Darwin and the theory of evolution as revealed in his masterwork, On the Origin of Species, published in 1859, little was known about the “bloody obvious” fact that offspring, to one degree or another, tend to reflect identifiable characteristics of their parents. Darwin’s certainty about the validity of “natural selection” as the core principle of evolution still left much uncertainty in his mind as to the actual mechanism of heredity – the passing along of biological traits. Notably mysterious to Darwin was the biological “mechanism” responsible for the significant changes and diversity that randomly occur within a species, thus setting the stage for natural selection to pass long-term judgement on the alternatives presented. Put another way: over the long-haul, natural selection favors genetic adaptations most favorable to survival in a given environment.
In 1866, merely seven years after Darwin’s milestone book, an obscure Austrian monk published a little-noted paper on experiments breeding pea plants he had been performing in his spare time within his abbey’s small garden. Using three well-known variations of these plants and inter-breeding them, he meticulously tracked his results. The three variations studied were color: green or yellow plants; flower: white or violet; and seed texture: smooth or wrinkled. In Mendel’s paper, he dealt not only with dominant and recessive characteristics of these variables, but, surprisingly, determined that they manifested themselves in numerical ratios that were most revealing as to the nature of biological mechanisms at work!
Gregor Mendel: The Father of Genetic Science
Mendel’s little paper was supremely important as the first documented revelation of DNA/genetics at work. He had just a few “offprints” printed (scientific terminology for the personal printing of a paper intended for presentation by its author). His findings were sent to the local chapter of naturalist bee-keepers in Brno, Austria, where it received scant attention or interest. Mendel’s work with pea-plants disappeared quickly into the shadows of history until his paper was discovered and publicized for its great significance by the famous English biologist, William Bateson, in 1902. Despite its delayed recognition after thirty-six years, Mendel’s genius nevertheless still provided sufficient impetus for the resulting cascade of discovery and knowledge which ultimately led us to Watson and Crick’s ground-breaking revelation of the DNA double-helix in 1953. And now, for better and for worse, we are close to possessing the incredible capability to understand and to actually edit our own genetic code.
Did Darwin Miss Early Access to Mendel’s Discoveries?
Historical accounts tell us of an offprint copy of his pea-plant experiments that Gregor Mendel purportedly sent to the great man, himself, Charles Darwin, shortly after Darwin’s book on evolution was published in 1859. Darwin had no knowledge of this Austrian abbey monk, Gregor Mendel – or what he was attempting, but everyone, certainly Mendel, knew about Charles Darwin after 1859. Whether fact or fanciful lore, this milestone scientific paper of Mendel’s on genetics/inheritance was supposedly sent by Mendel and sat, in offprint form, unread amid the stacks of books and papers in Darwin’s study at Downe House. There, it was purportedly discovered after Darwin’s death. Walter Isaacson mentions the incident in The Code Breakers, but I have heard that the account as told may merely be fanciful.
Mendel’s Rare Offprint for Sale: on the Internet!
With my long interest in the history of science, I am familiar with many of the great milestones of scientific discovery and their publications – their formal introduction to the scientific world and the public at large. One of the most memorable items I have ever seen appear for sale, either at auction or via those who deal in such things, came from a renowned bookseller in London some twenty-five years ago. He was offering one of the few of Mendel’s original offprint papers in existence for a then jaw-dropping sixty-four thousand dollars. The paper was said to be in very good condition. I recall how, even back then, I sensed the rarity and deep significance of that particular item. Being an amateur historian of little means, I could only imagine what it would be like to possess such a rare, important slice of scientific history. Who knows where that particular offprint resides today: possibly in some large university library collection. Is it possible that it might have been filed away, unread, by Charles Darwin, himself? One thing I do know about that particular item: the sixty-four thousand dollar price twenty-five years ago would barely be a down-payment in today’s collecting market. The nature of such ground-breaking scientific rarities will ultimately render them priceless – which is as it should be, it seems to me.
Were Darwin aware of Mendel’s work with pea-plants through Mendel’s paper, he would have been fascinated with the revelations. Darwin wrote often about the nature of heredity in his many books before The Origin. The concept of DNA molecules which are integral to genes and chromosomes were well beyond even Darwin’s long reach. He was convinced, however, that there were biologic hereditary entities at work which shape and define all living things. Darwin referred to them as “gemmules,” while remaining necessarily vague about their attributes and ultimate reality. Although Mendel was able to shed first-light on the “how” of heredity’s behavior, the biological nature of its agents remained to him a mystery, as was the case with Darwin.
Scientific Knowledge IS Power; Have We the Wisdom to Handle It?
Many key discoveries have occurred in the rich history of biology and cell biology. The treasure-chest of acquired knowledge is full of just what the name implies: treasure. That accumulation of knowledge concerning ourselves and the world of living things is perhaps the most significant of all testimonials to what is good and noble about us humans. In these recent pandemic months, when Covid 19 was sweeping the country, instilling fear and taking well over a half-million lives in the process, vaccines quickly appeared which worked exceedingly well in diminishing the threat of this virus. Not many years ago, effective vaccines would have taken years to develop, if at all. It is said that much of the necessary research necessary to neutralize Covid 19 had recently been done and utilized on the earlier HIV and SARS viruses and that the vaccine methodologies were literally “on the shelf” – ready to use on this class of virus. This recent and undeniable affirmation of the power of scientific knowledge is all we need to know about why we should pay heed to pure scientific research which is foundational to all technologies that prove useful to mankind.
Gene editing holds the promise of correcting (curing) some of nature’s cruelest maladies: sickle-cell anemia, Huntington’s disease, Tay Sachs, for example. Huntington’s is a spectacular example of how a simple DNA/gene coding mistake can condemn an individual’s adult future. Although direct human trials of gene editing medicine are necessarily very rare at this time, the process has already been proven successful on a patient with sickle-cell anemia. Along with the promise of positive advances in medicine comes the danger of mis-using genetic editing. Consider “designer-babies,” and let your imagination run wild.
I have heard the comment that there are two major scientific advances in recent history that point to the need for the strictest supervision of their applications in order to avoid horrific consequences. The first is Albert Einstein’s purely scientific discovery in 1905 that mass and energy are one and the same. That revelation, despite Einstein’s purely scientific motivations behind it, has resulted in global arsenals of nuclear weapons whose power to destroy everything and everyone on this planet requires the utmost vigilance. The second cautionary tale involves irresponsible gene editing which poses a different set of catastrophic scenarios, but, like nuclear energy, once “the genie is out of the bottle,” it would be virtually impossible to recapture and control it. It has long been my view that every advance in science and technology comes complete with a pairing of both advantages for humanity (if wisely utilized), as well as a price to pay if not. Today’s internet and social media are good examples of vast benefits being constantly offset by potential and actual problems. In the case of gene editing, the potential for good and for bad reach the highest levels. At risk, is the potential for joining nuclear energy as a technology for which the “genie let loose from the bottle” is an apt metaphor.
Months after the lone atomic bomb test held in 1945 at Los Alamos, code-named Trinity, and the subsequent atomic bombing of Hiroshima and Nagasaki, J. Robert Oppenheimer, the bomb’s chief architect was asked by reporters about the prospects for the international control of atomic energy. A memorable film clip which clearly reflects his deep regret, even disgust, burns itself onto the mind’s eye. His answer: “It’s too late; it should have been done the day after Trinity.”
The question remains as man probes ever deeper into nature’s secrets: will we be wise enough to use science and technology to our advantage, or will we allow technology to de-rail and destroy us?
It seems obvious that we must continue to uncover the miracles of nature, those obvious and lasting truths underpinning our human existence, not only to use them to our advantage, but to glean the wisdom and perspective contained, therein. It appears clear from what I read that the scientific community is well aware of its obligations regarding gene editing.