Old newspaper headline reads, Lab Technique Offers Visual Proof, Chromosome Photo Cut and Reassembled Old newspaper ad reads: The Medical Research Unit have a vacancy for a biologist, to work with a group concerned with the causation of tumors in man

Cytogenetics: the Forgotten Prehistory of Genomics

Old newspaper headline reads: Experiment may lead to race of giant humans

In May 1952, the same month that DNA's double helix was first photographed in Rosalind Franklin's lab, an article appeared in the Spartanburg Herald-Journal's Peach Edition – extolling the future of "polyploidy, a scientific method of increasing the quality of fruit by increasing the number of chromosomes in the growing cells".
Research had already yielded "apples twice as heavy and a third larger than standard varieties".

When this article was written, cytogenetics - the study of chromosomes' count, size, and shape - was about to enter its midcentury heyday. Japanese scientists had duplicated rice chromosomes decades earlier, and Barbara McClintock was identifying transposable elements within chromosomes, work which would later win a Nobel Prize.

Before I get too deep into history, I should acknowledge that cytogenetics labs are relevant today and karyotyping is used to confirm chromosomal disorders during pregnancy. This page is more about a span of time when cytogenetics was the primary frame to understand genetics, and subject to attention and hype in the media. Looking back, divining information from chromosomes without the ability to zoom in to genes seems so small.

If you are looking for a reference for cytogenetics' timeline, consider the journal Cytogenetics, which became Cytogenetics and Cell Genetics in 1973 and then the modern Cytogenetic and Genome Research in 2001. Or you can look at Google's Ngram Viewer.

1880s drawing of a cell, showing worm-like strings in the nucleus
cell from Chironomus spec., larvae, 1882

Chromosomes stand out
Chromosomes were named in the mid-19th century for their interesting coloring during staining. By the 1880s scientists could look at these colorful wormy chromosomes packed into the nucleus of a cell.

In the early 1900s, scientists reached a consensus that chromosomes were the mechanism of genetic inheritance.

Finding X and Y

Early research identified the X choromosome (1890-1901) and then Y chromosome (1905-1920) related to biological sex. They were noticed for behavior during meiosis, and not named not by shape. Everything was blobby at this point.

The Y chromosome still doesn't look like a Y, it just has shorter branches. Looking back at newspapers and books from the 1930s and 50s, it has an "odd size" or "peculiar, shorter", and it's only in the late 60s onward, after the spread of images of chromosomes looking more X-shaped during mitosis and meiosis, that you find misconceptions about a Y-shaped chromosome.
A completed Y chromosome sequence was not added to the Human Genome Project until 2022-23.

Incorporation into eugenics

Chromosomes become a major topic for scientists and in the eugenics movement.
In 1925, while announcing a new daughter in the Roosevelt family, one writer launches into a lesson on chromosome inheritance finishing with a prediction: "...with this child, so many wonderful chromosomes are assembled through every one of her eight great-grandparents, some of very great worth are bound to be passed on..."
In 1939, chromosomes are covered in the first half of an article about inheritance of musical talent.

Colchicine craze

In 1937, it's discovered that colchicine, an old treatment for gout, can affect the mitosis of plant seeds and cause a whole genome duplication (WGD). The resulting plants, with twice as many chromosomes per cell, sometimes grow larger seeds, grains, and fruits.
Farmers and gardeners experiment with spraying their plants with colchicine.
Newspaper articles at the time suggest giant humans could be coming.
In 1940 the Painesville Telegraph warns " Juggling chromosomes for the betterment of the plant kingdom is primarily a matter for the trained genetics engineer who knows the chromosomes with which he is working "

While World War II is beginning in Europe, the US government investigates colchicine's effects to accelerate growth of several crops.

Referenced in an episode of Quincy ME from 1979, legend has it that the Navy investigated growing polyploid hemp/marijuana for stronger rope. The episode's writers told the Associated Press that it was based on real history and a real problem; after seeing an ad for colchicine in High Times, they reported its toxicity to the FDA and EPA.
But did the research really happen? The most promising lead is a article by Haig Derman citing "Some remarks on the cytology of normal and colchicine- treated hemp-plants (Cannabis sativa L)" by W. P. Postma, both from 1940. Anyway if you are a screenwriter looking for a stoner Captain America based on true events, here you go.

1945 - End of World War II

By 1950, botanists have documented the number of chromosomes in crops as diverse as quinoa and Mexican tea.
They notice the number of chromosomes in varieties of rye have a common multiple, and that bread wheat is hexaploid - instead of two copies of each chromosome like in humans, it has six, combining three subgenomes which we now know combined about 9,000 years ago.
Colchicine returns with benefits for gardens and orchards. There are claims about polyploidy in animals, particularly Albert Levan's giant rabbits , which are now debunked.

Natural polyploidy is common in flowering plants, and it can occur by chance in farmers' fields. It can appear in a single variety, such as the Dalle Khursani chili pepper (100,000-350,000 Scoville units)
Some parts of our bodies have cells with two nuclei, but we are generally not considered polyploid.

Karyotypes and Intersex People

By 1952, researchers suggest images of the chromosomes known as 'karyotypes' or 'karyograms' will be groundbreaking for intersex people "where… the true sex of an individual is in doubt". Before this point, people who were intersex, or otherwise questioning or rejecting the gender assigned at birth, would get their hormone levels measured or request surgical exams, as in the case of civil rights leader Pauli Murray.

April 1953 - Watson and Crick publish the structure of DNA

It will be about 40 years before scientists can sequence a single yeast chromosome or a complete bacterial genome.

In December 1955 Joe Hin Tjio uses the lab's improvements to Giemsa staining to take the best photograph to-date of chromosomes in metaphase, showing that humans have 46 chromosomes (correcting the count by Theophilus Painter after over 30 years).

image of x-shaped chromosomes floating. It is not easy for a non-expert to see the claimed broken chromosomes. There is a citation of Warren W. Nichols' paper from 1963

Chromosome Damage?
From 1954 onward into the 60s, multiple cytogeneticists report that the measles virus breaks up chromosomes. Google will happily summarize these papers' results as current medical info. I tried to verify if this was still believed in the present, and a paper from the 1990s seems to validate them.

In the late 60s researchers also warn that LSD damages chromosomes (FDA video, Daytona Beach Morning Journal article) and that these issues would be passed down to children. According to a modern article in Science News, this was effectively debunked in 1971.

The birth of prenatal testing

In 1959, scientists realize that Down Syndrome is not a recessive trait but a chromosome duplication that "has nothing to do with heredity".

In 1961, an AP story postulates Someday You May Pick Baby's Sex. After several claims about male and female contraceptives, and X and Y sperm being different sizes (a popular theory of the time) the article rather humbly concludes with: "Why this happens, doctors don't know for sure. It is a sample of our ignorance."

Newspaper headline says: Cancer Research Centre Now Able to Study Chromosomes, most of the page is an ad for cigarettes
Saskatoon Star-Phoenix in Mar 23, 1962

Cancer and the Philadelphia Chromosome
In the 1960s, research continued in earnest on cytogenetics and cancer.
Researchers find a distinctively-shaped "Philadelphia chromosome" in many cases of leukemia. It takes over 10 years to identify this as a translocation of material between two chromosomes, and today we know the specific genes involved.

Testing Athletes

In 1967, Polish sprinter Ewa Kłobukowska is disqualified from participating in an international women's event based on chromosome results. Reporters at the time speculated on whether she had an extra X chromosome or mosaicism of X and XYY cells (Time magazine).
The incident leads the Olympics to adopt a confidential Barr Body test to screen athletes at the 1968 Winter Olympics in Grenoble, France and Summer Olympics in Mexico City.

Articles since the 1990s and the Olympics website generally agree that Kłobukowska has XX/XXY mosaicism and should not have been disqualified.

Newspaper headline reads: Criminal behavior said possibly due to cells
The Leader-Post, Saskatchewan, March 26, 1968

The Criminal Chromosome myth

In 1961 cytogeneticists documented the first patient with XYY chromosomes. Researchers were eager to karyotype institutionalized patients and see if various conditions could be explained with their chromosomes. Allen Bartholomew found multiple Australian prisoners with XYY chromosomes - in 1968 he testified in the trial of Laurence E. Hannell that "every cell in his body and the brain is abnormal". The argument was quickly repeated in cases in Paris, New York, and Los Angeles. Sirhan Sirhan's attorney requests a karyotype test.

Reports in the following year acknowledged that Hannell had other conditions warranting an insanity defense, and chromosomes were mentioned only once in the trial transcript; and a study found XYY "supermales" to instead be less aggressive. By 1971, criminologists reported it as A Modern Myth.

In 1970, Kenneth Royce began writing a series of crime and spy thrillers about The XYY Man as a compulsive criminal. By the 1976 TV adaptation (on YouTube) this element of the character seems to be downplayed, with one character asking "do you believe that theory?"

December 1968 - Apollo 8 orbits the moon

Chromosome Registries

In 1967, the New York Times reports a "Chromosome Service of the Soviet Union" has been set up, led by Alexandra Prokofieva-Belgovskaya, "one of the few Soviet scientists qualified to monitor the chromosome material of the cosmonauts". She was a former target of Stalin's pro-Lysenkoism purges.
A geneticist in Georgia (USA) begins collecting chromosomes from centenarians, hoping that the karyotypes will indicate how this proneness to longevity is passed from one generation to another
The New York State Chromosome Registry launches in 1968. In 1970, the Schenectady Gazette adds that registries were recommended by the WHO, and New York's is managed by the state's Birth Defects Institute.

The New York Times later reports on the foundation of an "Interregional Cytogenetic Register System".
Newspaper clip reads: Genetic Errors for Study, A national library of human genetic errors is being compiled. The newspaper includes a photo of a few scientists working together in the lab, including the director Gerald Prescott.

This 'registry' term is less popular today, but lives on in the "Chromosome 8p Registry & Biorepository" and "Chromosome 18 Registry & Research Society".

Normalization

By the 1970s "cytogenetics" and "karyotypes" are popular enough to appear in articles for a wider audience. A 1971 holiday puff piece quotes a Delbert Wiens, a karyology expert, on the number, shape, and size of mistletoe's chromosomes.
In 1975, a Florida hospital offers a class for new parents on aspects of pregnancy, complications, nutrition, exercises, family planning, cytogenetics, fetal development...

March 1986 - OHER and Los Alamos National Lab hold a workshop on the feasibility of "Sequencing the Human Genome"


Epilogue

To me cytogenetics sounds a little like biology's version of "cybernetics", a field which presaged the path that genomics would take. And its era deserves some more recognition, for both the highs and lows.
I'm struck by the realization that people 50-60 years ago had familiar plans around collecting a genetic database to understand aging and cancer. A lot of plans and promises like that didn't bear fruit.
Those polyploid peaches that I opened with were developed but quite never made it to Spartanburg. Despite research on their genetics, there don't seem to have been any commerical GMO peaches yet. Polyploid rice, which has usually turned out infertile and failed to catch on, is getting reconsidered with new approaches such as cross-breeding with wild relatives or gene editing.
The swift turnaround from discoveries in cytogenetics to testing, exclusion, and claims about violence is also remarkable. Barely a decade after science found the true typical count of human chromosomes, people were claiming that doctors could predict someone's criminality or longevity on a karyotype.

That's all that I can think to say about cytogenetics. I don't have other archival deep dives quite like this, but you could check out my podcast on Pro Se defendants at the US Supreme Court if that sounds interesting.
Please do reach out if I can write an article or a script on something!

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