Time Travel, Sea of Tranquility, and the History of Genetics

Tales of time travel have intrigued me since The Time Machine film scared the crap out of me at my cousin Ron’s ninth birthday party. Now The Time Traveler’s Wife, a novel from 2003 and film from 2009, has resurfaced in series form on HBO.

Emily St. John Mandel’s new novel Sea of Tranquility also follows a time traveler, across five centuries. The tale begins in 1912 in Canada and ends, if you look at time as linear rather than looped, in a dark, domed moon colony. The author wrote Station Eleven, so I was thrilled that she has a new book. Although it’s fiction, events during the middle time period unfold during a pandemic. It is an eerily familiar backdrop.

The Star Trek Futuristic Precedent

The #1 rule of time travel: you can’t go back and change anything. A poignant demonstration of this edict is “The City on the Edge of Forever,” considered by some to be the best installment of any Star Trek series ever. It was the penultimate episode of the first season, debuting on NBC on April 6, 1967 and written by Harlan Ellison.

Dr. McCoy ODs and beams down to a planet where he goes back in time and does something that changes history in a way that prevents the Federation of Planets from existing. Oops! Fortunately, Kirk and Spock follow to see what the good doctor is up to, and they all find themselves in 1930s New York City. Can they do something to reset the right timeline into the future, to save the Federation?

Of course, Kirk gets the hots for Joan Collins, playing social worker Edith Keeler. Sadly, the only way to preserve the correct future, in which the Federation will exist, is for Edith Keeler to get run over while crossing a street, which Kirk witnesses. You can get an “Edith Keeler Must Die” tee shirt here.

The message is clear: you can’t change the past.

In Sea of Tranquility, time traveler Gaspery-Jacques Roberts goes from the 25th back to the 23rd century, where he allows a famous novelist to survive a pandemic when he knows she was fated to die. And that sets into motion events that rip the fabric of time, causing a strange confluence of images to reverberate in various settings – the sound of a man playing a violin in an airship terminal surrounded by a forest. It all makes sense in the end.

A Genetic Connection

What does time travel have to do with genetics?

While reading Sea of Tranquility I began to imagine myself a time traveler, going back to the experiments and ideas that built the field of genetics.

I envisioned meeting Gregor Mendel in his garden and telling him about how today a human genome can be sequenced in a day, and DNA ancestry information held in a smartphone. And I realized that my thought experiment, marveling at Mendel’s ability to discern a law of nature from patterns of traits of pea plants, was opposite the way I look at the evolution of technology in my lifetime.

I’m so used to streaming and bingeing a TV series that network weekly drops are intolerable.

Pandora and Spotify vanquished iTunes, CDs, records (LPs and 45s).

I read novels on my iPad so I can cut and paste sections into posts. Can’t do that with a book.

I’m so used to my iPhone that the landline ringing is an increasing annoyance. It can’t be important.

I take the laptop I’m writing this on for granted. I wrote my PhD thesis on a typewriter at the dawn of word processing, thrilled to be able to replace the English letter ball with one bearing Greek letters to distinguish the alpha and beta chains of hemoglobin.

When it comes to the history of genetics, though, I think that the older experiments were the more brilliant. Knowing less tapped the powers of observation, imagination, deduction, synthesis, and generalization more.

From Mendel’s Peas to Double Helices

Gregor Mendel was an Augustinian friar and amateur botanist. He paid careful attention to variable traits, such as pea color, plant height, and whether pods are wrinkled or smooth. Mendel was the first to deduce the rules of logic that make it possible to predict inheritance patterns of specific traits.

Mendel’s rules are laws because they apply to any species that has two sets of chromosomes. Yet he had no idea what chromosomes or even cells were, let alone genes and DNA. But he was aware from other breeders that, in different species, some traits disappear in one generation and then reappear in the next. How did that happen?

From 1857 to 1863, Mendel set up crosses and cataloged traits through several generations of 24,034 plants. He perceived in the consistent ratios of traits in offspring that the parent plants had transmitted distinct units of information. He called them “elementen.”

Mendel published his findings in 1866, but few people read the paper. Then a trio of botanists independently read Mendel’s paper in 1901 and realized its power. Rediscovered, Mendel became known as the “father of genetics.” He died in 1884.

Discovering the Nature of the Genetic Material

Mendel’s insight, his ability to see patterns and deduce mechanisms, stands out because of how much he didn’t know. Other milestones in the history of genetics, to me, don’t carry the same punch.

My background is somewhat different from most folks who write about genetics, because I’ve been writing a human genetics textbook (for McGraw-Hill Higher Education) since 1993; I’m currently working on the fourteenth edition. While technology updates have come to dominate my coverage, I retain the historical milestones that have driven genetics to evolve into genomics. The highpoints still pepper my chapters, from which the following vignettes come. (Descriptions of the discoverers are in the links.)

Five years after Mendel released his ignored paper (1871), Friedrich Miescher published on his discovery of “nuclein,” the substance behind Mendel’s elementen. The name came from the fact that Miescher had found the stuff in the nuclei of white blood cells from pus on soiled bandages. It contained nitrogen and phosphorus, and he and others went on to find it in many other cell sources. Later, nuclein morphed into nucleic acid. As was the case for Mendel’s findings, few contemporaries appreciated the importance of Miescher’s discovery.

Yes, Miescher saw something unusual and described it, identified its parts. But that’s not quite equivalent to Mendel’s mental leap.

A year after the re-discovery of Mendel’s paper, another chapter in the story of identifying the genetic material was written. At the time, inherited disease was widely attributed to abnormal protein, perhaps because it was better studied than fats, carbohydrates, and nucleic acids. Inherited traits DO arise from proteins – but the nucleic acids RNA and DNA encode the proteins.

In 1902, Sir Archibald Garrod was the first to link inherited disease and protein. People who had certain inborn errors of metabolism, he noted, did not have certain enzymes. Then researchers noted links between heredity and deficient enzymes in other species: fruit flies with unusual eye colors, bread mold with nutritional deficiencies. Thoughts returned to Miescher’s discovery of nucleic acids, and the focus of experiments shifted.

Yes, Garrod linked two deficits. But that’s not quite equivalent to Mendel’s mental leap.

In 1928, Frederick Griffith took the first step to identifying DNA as the genetic material. He was studying deadly Strep bacterial pneumonia in the wake of the 1918 flu pandemic. He worked with two types of bacteria: rough versus smooth. The sugar-coated smooth bacteria were cloaked from the mouse’s immune system and caused the deadly pneumonia. In a clever series of experiments, Griffith demonstrated that smooth bacteria could pass their killing ability to rough bacteria, and that the bolstered bacteria passed on the new trait. But a bomb during the London blitz killed him before he could explore further.

What was Griffith’s “transforming principle?”

A trio of physicians, Oswald Avery, Colin MacLeod, and Maclyn McCarty, thought it might be a nucleic acid. Their experiments, also using Strep, seem simple in retrospect. Adding an enzyme that dismantles protein didn’t prevent turning the rough, vulnerable bacteria into smooth killers, but adding an enzyme that dismantles DNA did disrupt transformation. So, in 1944, they confirmed that DNA did it.

In 1953, Alfred Hershey and Martha Chase’s “blender experiments” confirmed that DNA is the genetic material and protein is not. They used E. coli infected with viruses that bind with their protein “heads” and inject their DNA. Hershey and Chase took advantage of the fact that protein contains sulfur but not phosphorus, and that nucleic acids contain phosphorus but not sulfur, and radioactively labeled each element. Blenders shook up infected bacteria to follow the labels and deduce what gets inside the cells – it was DNA.

Yes, Griffith; Avery, MacLeod and McCarty; and Hershey and Chase zeroed in on DNA as the genetic material, but they knew what to look for. That’s not quite equivalent to Mendel’s mental leap.

Watson and Crick famously assembled clues that others had discovered.

In 1929, Phoebus Levene identified the sugar deoxyribose and found that a DNA building block consists of equal parts deoxyribose, a nitrogen-containing (nitrogenous) base, and a phosphorus-containing component. The sugar-phosphate part was always the same, but the nitrogenous bases were of four types, so they could carry information in their sequences. But for years the bases were thought to be present in equal numbers, limiting their capacity.

In the early 1950s, Erwin Chargaff showed that DNA in several species contains equal amounts of the bases adenine (A) and thymine (T) and equal amounts of guanine (G) and cytosine (C). That was a key clue.

Then Maurice Wilkins, Rosalind Franklin, and Raymond Gosling bombarded DNA with X rays, creating patterns revealing what James Watson called “a beautiful helix!”

Yes, Levene, Chargaff, Wilkins, Frankin, and Gosling provided compelling puzzle pieces for Watson and Crick to put together. But everyone’s insights and discoveries built on those that came before. That’s not quite equivalent to Mendel’s mental leap.

Genetics Becomes Genomics

The 1980s saw identifying signposts in a human genome and discovering the genes behind a slew of diseases. People began to talk about sequencing “the” human genome in the mid 1980s – I attended some of those meetings.

The first human genome sequences were published circa 2000-2003, having taken over a decade to do (here’s a timeline). Now human genomes are sequenced in under a day, and a huge effort has been devoted to cataloging human genome diversity and describing the human “pangenome.”

We’re still trying to decipher what the 20,000 or so human genes do. But today, with decades of data accruing, algorithms and machine learning augment human brains by recognizing patterns in DNA sequences.

If a gene specifies a protein that has 7 loops, the protein probably resides in a cell membrane.

If a specified protein is blobby and folds around an iron atom, it’s a globin and carries oxygen.

If an encoded short protein wraps around a zinc atom like a finger, it’s a transcription factor.

On and on it goes, a vast availability of databases and tools to help us see the patterns, to tease meanings from genes.

But bioinformatics is not quite equivalent to Mendel’s mental leap.

I can’t help but wonder what time travelers a century hence will think of the state of the field of human genetics today.