The History of Microscopes

Gabriellebirchak/ April 13, 2020/ Modern History, Post Classical

Galileo’s Occhi­oli­no

On April 13, 1625, Galileo’s friend Gio­van­ni Faber, wrote a let­ter to Prince Fed­eri­co Ange­lo Cesi about this fas­ci­nat­ing tool that could mag­ni­fy small items. He referred to it as the “micro­scope” that is derived from the Greek words micron, which means small, and skopein, which means to look at. That same year, Cesi, along with sci­en­tist Francesco Stel­lu­ti pub­lished their work Api­ar­i­um. This body of work includ­ed their micro­scop­ic obser­va­tions of three bees. It was the first pub­lished work that depict­ed micro­scop­ic obser­va­tions of bio­log­i­cal structures. 

Though some peo­ple refer to COVID-19 as the invis­i­ble ene­my, the virus is far from invis­i­ble. We know this because we have micro­scop­ic images of the virus, and we’ve seen the illus­tra­tion of the virus as that fuzzy gray ball with red spikes. The illus­tra­tion is a bril­liant 3D ren­der­ing what it kind of looks like. The par­tic­u­lar graph­ic that I’m refer­ring to is the fuzzy gray ball with red spikes. It is an illus­tra­tion and not what the virus actu­al­ly looks like. This phe­nom­e­nal arti­cle, writ­ten by Robert Britt, explains the com­po­nents of the illus­tra­tion and indi­cates how much more dan­ger­ous this virus is com­pared to oth­er sars-relat­ed illnesses.

COVID-19

But in actu­al­i­ty, the virus does­n’t real­ly look like a fuzzy gray ball with red spikes. It’s actu­al­ly col­or­less. This excel­lent arti­cle in Wired Mag­a­zine shows an image of Luke Jer­ram’s viral crys­tal sculp­ture that rep­re­sent virus­es like Coro­n­avirus. If you want to see more of Jerram’s gor­geous sculp­tures, his web­site is at https://www.lukejerram.com/

The Nation­al Insti­tute of Aller­gy and Infec­tious Dis­eases Rocky Moun­tain Lab­o­ra­to­ries in Hamil­ton, Mon­tana, post­ed some of the first images to emerge of the virus. The images were cap­tured with an elec­tron micro­scope that scans and trans­mits the image.

After they obtained the image of COVID-19, micro­scopist Eliz­a­beth Fish­er pro­duced the images. Then their Visu­al Med­ical Arts Depart­ment col­orized the images. The col­or­ing is there so that we can actu­al­ly see them and under­stand what they look like.

SARS-CoV­‑2 (yel­low) among human cells (pink). (Image: © NIAID-RML)

THE HISTORY OF THE MICROSCOPE

As we all know, micro­scopes are made from glass. We have evi­dence from the East­ern Mesopotami­an and Egypt­ian regions of some of the first man-made glass that dates back to 3500 BCE.

By 700 BCE, Assyr­i­ans wood man­u­fac­tur­ing lens­es that could be used as mag­ni­fy­ing lens­es. One was found in 1850 by Austin Hen­ry Layard in mod­ern-day Iraq in an area that was for­mer­ly called Nim­rud. Today, you can see the Nim­rud lens at the British Muse­um in Lon­don online.

By Geni — Pho­to by user:geni, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=13302965

Around 300 BCE Euclid wrote his work Optics, which cov­ered the geom­e­try of vision and began to set the ground­work for see­ing things through glass. This body of work was fur­ther stud­ied by many sci­en­tists there­after. Com­men­taries were writ­ten by famed math­e­mati­cians and sci­en­tists Ptole­my, Theon (who was Hypatia’s father) and Abū ʿAlī al-Ḥasan ibn al-Ḥasan ibn al-Haytham (also known as Alhazan). 

By 500 BCE, glass was being man­u­fac­tured and sold for prof­it. By the sec­ond cen­tu­ry BCE, ear­ly sci­en­tists in Chi­na were using micro­scopes made of a lens and a water-filled tube. 

In the 13th cen­tu­ry, Rodger Bacon exper­i­ment­ed with lens­es and sug­gest­ed that they could be used as eye­glass­es. This con­tributed to the devel­op­ment of the micro­scope. Lens­es at this point real­ly only had a mag­ni­fi­ca­tion between six and ten diameters. 

In the 1590s, the micro­scope made sig­nif­i­cant progress. Zacharias Janssen and his son Hans, who made glass­es, dis­cov­ered that when they placed sev­er­al lens­es inside of an eigh­teen-inch tube, they could mag­ni­fy an object. How­ev­er, the mag­ni­fi­ca­tion of the micro­scope was just nine diam­e­ters. Still, this was groundbreaking! 

From this point for­ward, the devel­op­ments came quick­ly. Galileo Galilei was able to use his tele­scope to see small objects up close. He then devel­oped a com­pound micro­scope using a con­vex and a con­cave lens that he called the Occhi­oli­no, which means “lit­tle eye.” How­ev­er, Galileo’s inven­tion was not actu­al­ly con­sid­ered a com­pound micro­scope because it had a con­cave lens.

In 1622, Cor­nelius Drebbel pre­sent­ed his inven­tion of the micro­scope in Rome. It was the Kep­ler­ian micro­scope, which was also one of the first com­pound micro­scopes that held a con­vex objec­tive AND a con­vex eye­piece. Here is where the sto­ry gets inter­est­ing. (It’s kind of like a Tes­la and Mar­coni sto­ry.) In 1622, Drebbel, who lived in Lon­don, sent his son-in-law Gio­van­ni Kuf­fler, off to sell the microscopes. 

Kuf­fler first trav­eled to France, where he met Nico­las Peiresc and gave him a Kep­ler­ian micro­scope. Then Kuf­fler trav­eled to Rome, where he met the Car­di­nal of San­ta Susana. He gave the Car­di­nal two Kep­le­ri­ans but nev­er had the chance to explain to the Car­di­nal how they worked because Kuf­fler died while in Rome.

After Kuf­fler died, Peiresc sent his micro­scope off to the Car­di­nal along with a let­ter explain­ing how the Kep­ler­ian worked. In this let­ter, he described the items that he observed while using the micro­scope. How­ev­er, for some rea­son, the Car­di­nal nev­er received the package.

Then in 1624, Galileo had trav­eled to Rome to meet the Car­di­nal. While Galileo was in Rome, the Car­di­nal asked him for help try­ing to get the Kep­ler­ian micro­scope to work. Since Galileo had an idea as to how it worked, he was able to explain Drebbel’s inven­tion to the Car­di­nal with­out any prob­lem. In the process, Galileo dis­cov­ered that Drebbel’s design used two con­vex lens­es. And just like that, Galileo fig­ured out how Drebbel’s inven­tion worked!

So, a few months lat­er, on Sep­tem­ber 23rd, 1624, Galileo sent a new Occhi­oli­no to Prince Fed­eri­co Cesi, Who was a poly­math and found­ed a sci­en­tif­ic Soci­ety known as the Accad­e­mia dei Lin­cei. Includ­ed with the Occhi­oli­no wasa let­ter that described lens­es and men­tioned the efforts he took to grind them down to the cor­rect cur­va­tures. What is inter­est­ing about this let­ter is that it was almost ver­ba­tim to the same let­ter that Drebbel wrote to Peiresc in 1622![i] 

So much like today’s delet­ed tweets that nev­er go away, Drebbel’s let­ter resur­faced long after this to lead some his­to­ri­ans to ques­tion who real­ly invent­ed the com­pound microscope! 

Cesi knew he was on to some­thing. On April 13, 1625, Galileo’s friend Gio­van­ni Faber wrote a let­ter to Cesi about the fas­ci­nat­ing tool that could mag­ni­fy small items. In this let­ter, Faber referred to it as the “micro­scope,” which is derived from the Greek words micron, which means small and skopein, which means to look at. Hence, April 13 is the 395th birth­day of the word microscope.

That same year, Cesi, along with sci­en­tist Francesco Stel­lu­ti pub­lished their work Api­ar­i­um, which includ­ed their micro­scop­ic obser­va­tions of three bees. It was the first pub­lished work that depict­ed micro­scop­ic obser­va­tions of bio­log­i­cal struc­tures. This was the begin­ning of 395 years of micro­scope development.

In 1665, Eng­lish physi­cist Robert Hooke, using his micro­scope to look at tis­sue, coined the term “cells.” 

Around 1674, Antony Van Leeuwen­hoek (a Dutch sci­en­tist) emerged on to the scene with lens­es that he cre­at­ed by grind­ing and pol­ish­ing a glass ball into a lens. These mag­ni­fy­ing lens­es had 270 times the mag­ni­fi­ca­tion. With his ground­break­ing lens­es, he was able to see and describe liv­ing cells, such as bac­te­ria, blood cells, and yeast. 

Then by 1846, Carl Zeiss was mass-pro­duc­ing these micro­scopes. How­ev­er, his mass pro­duc­tion real­ly picked up when physi­cist Dr. Ernst Abbe became the research direc­tor at Zeiss Opti­cal Works. While Abbe was at Zeiss, he cre­at­ed the Abbe sine con­di­tion, which is an opti­cal for­mu­la. This for­mu­la presents the require­ments that a lens needs to sat­is­fy to form a sharp image, free from blur­ring. Abbe was the brains of this oper­a­tion and set Zeiss up for suc­cess. As a result, Zeiss became the dom­i­nant micro­scope man­u­fac­tur­er of the nine­teenth century.

Mary Somerville

In 1869, Mary Somerville pub­lished her work mol­e­c­u­lar and micro­scop­ic sci­ence. Then, in 1897, Amer­i­can cytol­o­gists and zool­o­gists Kather­ine Foote and Ella Church Stro­bell, who worked as research Part­ners in the field, ini­ti­at­ed the prac­tice of pho­tograph­ing micro­scop­ic research sam­ples. Addi­tion­al­ly, they cre­at­ed a new tech­nique of observ­ing thin mate­r­i­al sam­ples in cold­er temperatures.

Final­ly, in the 20th cen­tu­ry, in 1931, Ernst Rus­ka and Max Knoll designed and built the first Trans­mis­sion Elec­tron Micro­scope, oth­er­wise known as the first TEM. The TEM required elec­trons, not light, to see an object. 

The devel­op­ment of micro­scopes allowed us to see and ana­lyze micro­scop­ic objects that we nev­er thought pos­si­ble. In 1932, Frits Zernike devel­oped phase-con­trast in illu­mi­na­tion that allowed us to image trans­par­ent sam­ples. He won the Nobel Prize for this in 1953.

In 1957, Mar­vin Min­sky patent­ed the con­fo­cal micro­scope, which uses a scan­ning pin­hole of light to pro­vide a high­er res­o­lu­tion in scanned images.

In 1967, Erwin Wil­helm Muller cre­at­ed a micro­scope; it was an atom probe and was able to iden­ti­fy the chem­i­cal make­up of indi­vid­ual atoms.

In 1972, God­frey Hounsfield and Allan Cor­ma­ck devel­oped the first Com­put­er­ized Axi­al Tomog­ra­phy CAT scan.

Sev­er­al CT scans show­ing a 1 CM Col­loid cyst in the 3rd ven­tri­cle.
By Time­hold­er — Own work, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=23203218

In 1981, Gerd Bin­nig and Hein­rich Rohrer devel­oped the first Scan­ning-tun­nel­ing microscope.

Five years lat­er, in 1986, Bin­nig, along with Calvin Quate and Christoph Ger­ber, invent­ed the Atom­ic Force Micro­scope. This same year, Rus­ka, Bin­nig, and Rohrer joint­ly won the Nobel Prize in Physics for their work. 

In 1988, Kingo Itaya invent­ed the Elec­tro­chem­i­cal Scan­ning tun­nel­ing microscope.

In 1991, the Kelvin Probe Force micro­scope was invented.

In 2009, Dame Prat­i­b­ha Gai made ground­break­ing progress with her inven­tion of the In situ Atom­ic res­o­lu­tion envi­ron­men­tal trans­mis­sion elec­tron micro­scope, known as the ETEM. Her micro­scope allowed for obser­va­tions of chem­i­cal reac­tions at an atom­ic scale. Gai decid­ed not to patent her inven­tion in order to fur­ther the advance­ment of science.

So, by 2010 researchers at UCLA using a cryo-elec­tron micro­scope were able to see the atoms of a virus.

Priyam­va­da Acharya, Duke University

As of this month, Priyam­va­da Acharya and her team at Duke Uni­ver­si­ty are using their cryo-elec­tron micro­scope called the Titan Krios to observe and deter­mine the struc­tures of the coro­n­avirus spike pro­tein, so that they can under­stand how the virus enters human cells. The Titan Krios trans­mis­sion elec­tron micro­scope gath­ers images to cre­ate a 2D and a 3D char­ac­ter­i­za­tion of bio­log­i­cal samples.

Now, in our cur­rent age, we have the abil­i­ty to see when the virus enters a healthy cell! That’s the pow­er of micro­scopes! That’s the pow­er of science!


[i] Clara Sue Ball. “The Ear­ly His­to­ry of the Com­pound Micro­scope.” Bios 37, no. 2 (1966): 51–60. Accessed April 12, 2020. www.jstor.org/stable/4606667.

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