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The New Year is almost upon us. And to ring in 2021, we wanted to celebrate some of the greatest minds in science. Folks who have contributed to our understanding of the world, and in some cases saved lives along the way. 

So sit back, relax and get ready to be blown away by some of the most significant researchers in history. First to go way back in the SciShow archives, and pretty far back in actual history, we have got Marie Anning, whose scientific career got started because she happened to have the coolest backyard ever.

Here is 2014 Hank with more. 

Mary Anning was born in 1799 to relatively poor parents on the Southern coast of Britain. Their backyard ran into the cliffs at Lyme Regis; an area now renowned for its wealth of amazing Jurassic-era fossils. Back then fossil collecting was done by amateurs, sometimes as a hobby other times for profit, but not really for science. It is important to note that when Anning began collecting fossils the prevailing scientific theory was that they were just preserved remains of existing animals. The idea that an animal had ever gone extinct had been proposed but wasn't widely accepted. 

Anning's father Richard was a cabinet-maker, but he dabbled in fossil collecting and passed that love onto his daughter. When Mary was 11 her father died, so she and her mother and her brother began selling fossils to make ends meet.

Now the best time to collect fossils at Lyme Regis was right after a land slide when new fossils might have been exposed, but that was also of course the most dangerous time to be on the cliffs; though it was not until she was in her 30's that she was caught in a land slide. 

She survived, but her dog Tray wasn't so lucky. 

Over time Mary taught herself the basics of anatomy using animals that no one had ever seen alive and this helped her become an expert in the science and the art of preparation; the technique of removing rock from around a fossil to expose the specimen inside it.

This sounds maybe easier than it is, it is actually like separating rock from a very slightly different rock. 

The fossils she and her family found and prepared eagerly sought and not only by museums and scientists, but by European nobles many of whom had substantial private collections of fossils and other curiosities from around the world.

And Anning made many significant discoveries at Lyme Regis. At the tender age of 10 Mary and her brother discovered the first specimen of Icthyosaurus; an aquatic fish-like reptile, ever recognized by the London scientific community.

Years later she solved the mystery of what scientists at the time called Bezoar Stones wired rocks that were found inside some fossil animals. Anning had seen enough of these to have noticed patterns like that they were often spiral shaped and were usually found in the lower abdomens in Icthyosaurs. Having the presence of mind to dissect a few samples of these stones, Anning discovered bones inside of them. The fossil remains of fish and their scales, sometimes even smaller Icthyosaurs. 

She realized that Bezoar stones were actually fossilized feces. Now known as Coprolites which became hugely important in understanding the structure of prehistoric ecosystems. 

She also discovered the first Pterosaur fossil ever found outside of Germany along with various important fossil fish including a perfectly preserved cuttlefish with ink sacs intact. 

But perhaps her most important find came in 1824 when she came across the nearly intact remains of a strange animal 10 meters from head to tail with an enormous neck. 

When a famous French palaeontologist saw Anning's sketches of the specimen he dismissed it as a fake, but further study would prove that she had found the first Plesiosaur; an early four-finned marine reptile that didn't resemble any animal found before. 

This "Grand Fossil Skelton of Lyme Regis" became an object of international fascination, and Anning's work on it had her communicating regularly with the most prominent scientists in the field. 

Unfortunately, the structure of society at the time made it impossible for Anning to publicly participate in science, and most of her discoveries ended up being published by men that she collaborated with.

Let's leap forward a few million years from the Mesozoic to the Space Age. One of the biggest challenges of landing on the moon was figuring out the whole "how to program a computer" thing. And while plenty of people were involved in this, a big one was Margaret Hamilton. Without her, that famous "One Small Step" speech from Neil Armstrong, may not have happened at all. 

Here is another one from Hank.

So you are on your way to the moon. It has been a long trip, and just as you are finally about to land your spaceship, the computer starts to spit out error message after error message. This is uh an extremely non-ideal situation, and sounds really terrifying and it is exactly what happened to astronauts on Apollo 11; the first mission that landed humans on the moon. In the end, the astronauts landed safely, and Margaret Hamilton, a computer scientist who worked for NASA in the 1960s and 70s was why.

Margaret rose through the ranks to eventually become the head of the Apollo flight software development team and a pioneer for women in STEM fields.

Hamilton has spent her life focused on errors; how to prevent them and how to keep everything running when they come up. And her approach is what saved Apollo 11 from having to abort the mission. 

Hamilton was born on August 17th, 1936 in a small town in Southern Indianna. In 1958 she earned a Bachelor's Degree in Math in Earlham College with a minor in Philosophy. She taught in a high school for a couple of years and then worked in a few different 

  

MIT programming labs. Eventually, Hamilton planned to pursue a PhD in abstract math, but then she got an offer. A lab at MIT was looking for programmers to work on the computer that would take humans to the moon. So she took that job.

Back then, programming software (the code that tells computers what to do) was not really a thing that people went to school for. The field was pretty new and developing quickly, so Hamilton like a lot of early computer scientists, learned on the job. 

One of her first assignments was for an unmanned mission and it involved designing a program that would tell the computer what to do if the mission aborted. 

According to Hamilton, NASA execs gave her the assignment because they did not think it was likely that the mission would abort but, then it did, and the computer ended up using her program. 

To write that program, Hamilton had to consider what would happen if a mission failed, like if a key instrument decided not to work or the craft ran out of fuel. It was a theme that continued to come up during her time at NASA and throughout her career.

Like when it came time to program the computer for Apollo 8, the first manned mission to orbit the moon. The software team tested their designs using simulators that would run the programs as though they were being used on the mission. While one of these tests was simulating the spacecraft in flight, Hamilton's 4-year-old daughter, whom she'd brought to work that day, accidentally started a program that was meant to be used pre-launch and the simulator crashed. 

Hamilton realized that this was an error that could easily come up during the mission itself if an astronaut pushed the wrong button by accident. She wanted to program in a workaround but first, she needed clearance from NASA, and they said no. They did not think an astronaut would actually make that mistake.

Then Apollo 8 launched, and 5 days into the mission one of the astronauts, yes, pushed the wrong button and started the pre-launch program which erased part of the data that the computer needed to get the astronauts home. 

It took NASA engineers 9 hours to come up with the fix which involved sending a replacement set of data to the Apollo computer. But the problem could have been prevented if Hamilton had been allowed to plan for it. 

And then came Apollo 11.

The errors that cropped up just as the crew was about to land, came from the fact that the computer was being asked to do more calculations than it could handle. The extra demand came from the

Rendevous Radar which the landing module was using to keep track of the command module that stayed in orbit around the moon. 

The program for the radar hadn't been set up properly and it was asking the computer to perform 6400 operations per second, about 13% of the total processing power. 

That is not so much - except that the computer needed to land on the moon took up 90% of its processing power so it was overloaded. Luckily Hamilton and her team designed Apollo's computer to take priorities into account which was unusual for computers at the time. 

Instead of trying to do all of the tasks it was assigned in order - which in this case would have crashed the computer - it responded to an overload by focusing only on high-priority tasks. 

Landing on the moon was rated a much higher priority than messing with the Rendevous Radar, so the computer concentrated on landing, and the astronauts made it to the moon's surface. 

After Apollo 11 Hamilton continued designing software for NASA, working on the computers used for the rest of the Apollo missions, as well as Sky Lab; America's first space station. 

She's now the CEO of Hamilton Technologies, a company she founded in 1986 which provides a way for software engineers to integrate different programs so they act like one big system.

Integrating the programs this way helps prevent errors that can come from interfacing when programs exchange information.

Nearly 47 years after Apollo 11 Margaret Hamilton is still working on ways to get rid of software bugs.

Prioritizing high-priority tasks so you don't overload - also sounds like good work advice, come to think of it. From getting bugs out of software to getting bugs out of people, we turn to Gertrude Elion. The researcher who changed drug development forever. Whether you know someone with an autoimmune disease or have taken a drug to fight a virus, you probably have her to thank. This time, we've gone to Michael to tell us more. 

Back in 1944, scientists were only just beginning to suspect that DND was our genetic material. That's the year Gertrude Elion first started studying nucleotides; the chemical building blocks that form DNA. 

Over the next five decades, Elion became a leading expert on nucleotides,

and her outside-the-box thinking led to methods that totally transformed the world of drug development; including life-saving therapies we still use today.

Gertrude Elion was born in New York City in 1918, the daughter of Eastern European immigrants. The year she finished high school, she watched her grandfather succumb painfully to cancer. His death inspired her to study chemistry in college, and eventually earn a  Master's degree. 

There weren't a ton of research jobs available during the Great Depression, particularly for a woman. But after World War II broke out, she scored a position in the lab of a guy named George Hitchings. 

Hitchings had this idea that if you could understand a biological process, you should be able to use that information to design chemicals to disrupt that process. 

This idea might seem obvious now, but that's just because it's how we like to develop drugs today. At the time, this rational approach to drug design, as it came to be called, was new and pretty radical. 

See, in the mid 1940's most of the drugs that were available were either based on plant compounds that people had been using for millennia like Asprin, or they'd been discovered by accident- like Penicillin.  

But Elion and Hitchings wanted to take a more deliberate approach, and there were 2 key reasons why nucleotides seemed like a good place to start. 

One, all cells need them to divide since dividing means doubling your DNA and DNA means nucleotides. 

And two, certain bad cells like cancer, parasites and bacteria divide way faster than healthy cells. This makes them especially hungry for nucleotides. If you had a way to exploit this hunger, you might be able to fight all those things. 

The problem was, nobody knew much of anything about how cells make or use nucleotides. One of Elion's first assignments at her new job was to start figuring all of this out. So she synthesized a bunch of chemical analogues that were similar to nucleotides, or things that cells needed for making nucleotides. The idea was to see what cells would do with these impostor compounds. 

Some of the analogues had key chemical differences that made cells unable to use them like normal nucleotides. They were a biochemical dead-end, and they would gum up the works. Essentially blocking a cell's ability to make DNA or RNA. 

Which is exactly what Elion and Hitchings were looking for in a drug. But they had to make sure it was not too toxic to people. 

The first

breakthrough came in 1951 when Elion synthesized 6-Mercaptopurine, or 6-MP.

It's one of those dead-end molecules and is especially good for stopping out-of-control immune cells. It was a huge step forward in treating childhood leukemia and it opened the door to new ideas for treating cancer in general. 

In testing 6-MP and related molecules, Elion started to piece together that different cell types and cells from different species responded differently to some analogues and that's the key to making drugs like these work. 

Once she found a promising lead, she would design slightly different compounds to try to exploit some of those differences. Her approach to synthesizing them was novel as well. On top of that, she was among the first to follow what happened to drugs in the body - and used that information to design drugs that were more specific, less toxic and more effective. 

All of these approaches, in combination, led to lots of new discoveries about nucleotide metabolism and they led Elion to treatments for an incredibly diverse set of problems including malaria, gout, tissue rejection, and autoimmune diseases.

Later in her career, she showed that it was possible to develop highly effective drugs for viral diseases. In the 1960s, most of the research world, including Hitchings, her partner, believed that since viruses used human cells to replicate, it would be impossible to develop a drug that would disrupt viral replication without harming the human host.

But Elion proved them wrong in a big way. She connected the dots between several studies, some hers, some from another lab and realised that modified nucleotides could block viral replication. She followed the lead and developed Acyclovir.

It's a compound that interferes specifically with the nucleotide-making enzyme from the herpes virus but not the human version of that same enzyme.

And this work paved the way for AZT, the first effective anti-retroviral drug in the fight against HIV and AIDS. In fact, it was scientists from Elion's research team who developed AZT after her official retirement.

Not only are AZT, 6-MP and other drugs Elion helped develop still in use today, the World Health Organisation counts them among the safest most effective drugs available. But beyond the drugs themselves, it was Elion and Hitching's contributions to the process of drug discovery that had the greatest impacts.

Once they showed that their process worked, that you could rationally build drugs from scratch, other drug companies around the world started using it.

And that's what earned them a Nobel prize. Elion and Hitchings along with co-awardee James Black received the Nobel prize in medicine in 1988 for their contributions to the field of drug development. It's rare that a half-century of toil earns such recognition, but no one can argue that it's not well deserved, and as long as we continue to use the drugs she designed, Elion's contributions will continue to improve the lives of people everywhere.

Now, when you think of great scientists, people in fields like medicine and engineering might come to mind pretty easily, but how about entomology? In the early 1900s Charles Henry Turner came on the scene and taught the world that insects are far more complex than we were giving them credit for.

Here's one more from Hank. I swear, we don't intentionally have him host all of our 'Great Minds' episodes.

Scientists used to think bugs were just reflexive machines, incapable of true decision-making or learning. Now, of course, we know that's not true. Insects are complex, cognitive creatures, and Charles Henry Turner, a researcher and school teacher who was possibly America's first black entomologist, played a big role in helping the scientific community realize that.

His work laid the foundation for what we know about insect behaviour - knowledge which has improved our understanding of everything from ecology to neuroscience. Nowadays it's common to see scientists researching the minds of bugs, like studying learning in bees to figure out how to increase crop pollination or simulating fly brains to understand how neural activity determines decision-making.

But back at the dawn of the 20th century biologists and psychologists alike believed that insects simply were not capable of that kind of thinking. They believed that all insect behaviour could be explained by specific responses to specific stimuli.

Like one American physiologist wrote that "caterpillars were machines enslaved to the light". But Charles Henry Turner thought there was much more to them than that and he ended up being right.

Turner was born in Ohio in 1867, two years after the American Civil War ended. And from an early age, he took an interest in insects and other animals. He reportedly read book after book after book about bugs. But books never seemed to sate his curiosity, so he began to study the natural world around him too.

After graduating first in his high school class he went on to earn his bachelor's and master's degrees at the University of Cincinnati, determined to have a scientific career. And his research was already starting to make waves. Like in 1892 (the same year he earned his master's), he published a summary of his thesis in the prestigious academic journal Science, which may have been the first Science paper from a black scientist.

And Turner was just getting started: by the time he got his PhD in 1907, he'd published roughly two dozen papers. Still after obtaining his doctorate, he couldn't get a professorship at a well-respected research university probably because he was black. So in 1908, he accepted a teaching position at Sumner High School in St. Louis with a starting salary of $1,080 a year. That meant his equipment and resources were limited and there would be no undergraduate or graduate students to help him conduct research.

But nothing could quell his insatiable curiosity. His research ended up showing that insects and other animals can perceive their worlds much like we do. And the way they behave in response is surprisingly thoughtful. For instance, in 1910 and 1911 he published conclusive evidence that honey bees see colours and patterns and they use that information to make foraging decisions. That might seem like a pretty obvious conclusion now since we are aware of how flowers can shape pollination activity. But at the time scientists questioned if bees could even see in colour, let alone recognise patterns. What's more, Turner's clever experiments demonstrated that these insects can learn too.

See, in his experiments, he placed food for the bees in uniquely coloured and patterned containers. Once the animals discovered which container had the treat they would seek out any container with the same colour or pattern. Then he changed which containers contained the food and it didn't take long for the bees to switch to a new go-to vessel, showing that they had learned from experience.

And Turner also recognised that bees weren't special in their ability to learn.

In one experiment, he trained cockroaches to behave totally unlike cockroaches and avoid darkness.

He also conducted what many think were the first Pavlovian conditioning experiments in insects. That's where one stimulus is paired with another to create a new, learned response to the original stimulus. A technique, of course, made famous by Russian physiologist Ivan Pavlov.

Turner was trying to see if moths can hear airborne sounds. Which, like with honey bee colour vision, was debated at the time. So, he contained moths in such a way that he could see their wings move but they couldn't fly away. Then he played different sounds at them and recorded what happened. Most of the moths reacted very obviously to the various whistles and pipes he played, demonstrating that they could, indeed, hear.

The trouble was, one species didn't and he wasn't sure if that was because the moths couldn't hear, or if they just didn't care about the sounds. So, he took those nonchalant moths and he played a particular sound while handling them roughly. Lo and behold, after several bouts of this, the moths started to try and flee whenever he played that tone all by itself.

So, they could hear it they just had no reason to react until it meant they were going to get roughed up. And they learned to have a different response to the sounds over time. That is textbook Pavlovian conditioning!

Those are just some of Turner's contributions to our understanding of animal behaviour. He kept conducting his research until his death in 1923.

He published 41 papers in his 15 years at Sumner High, all while teaching high schoolers chemistry, biology and psychology.

That's more than 2 papers per year, on average.

Which, for context, is higher than most of his contemporaries at colleges and universities. And Turner's clever experimental protocols continue to receive praise today.

Especially since his experiments were some of the first animal behaviour studies to employ solid controls. His foundational research went on to be cited by zoologists, entomologists and psychologists that essentially established the field of comparative psychology.  And now that field is helping us figure out how neurons really work, and how cognition happens in animals of all kinds; from the humblest of bugs to human beings. So, it's fair to say that Charles Henry Turner helped start a revolution in how we think about thinking.

And all because he took the time to really observe the world around him including species that many others had overlooked.

This really feels like a reminder that there is so much to learn about, no matter what you're interested in.

So for the last episode, we'll switch fields one more time to tell the story of a doctor who made work that much safer.

Here is Stefan with more.

The late 1890s and the early part of the twentieth century were characterised by rapid industrialisation. With a huge growth in low-wage factory jobs. And these factories were incredibly unsafe.

Employees working with dangerous chemicals could expect to come home covered in them and people were even locked into their places of work. And these jobs came with illness and conditions that were considered unavoidable occupational risks. But if you wanted your children to eat you'd take those risks.

Enter Dr. Alice Hamilton, who asked how can we mitigate those risks to keep people safe and healthy at work.

Alice Hamilton was born in 1869, which you may recognise as a time with very few women represented in medicine. But Alice had made up her mind when she was a teenager that that's what she wanted to do.

So, after taking lots of extra anatomy classes and sweet-talking her father into letting her go, she enrolled at the University of Michigan's medical school and got her M.D..

After doing her residencies she decided that she'd rather do research than open a practice so she went to Germany to study bacteriology.

And there she had to agree to make herself invisible in order to attend lectures. A process involving a lot of sneaking into seats that were carefully hidden in the backs of lecture halls.

After coming back to the US she lived and worked at Chicago's Hull-House. A so-called social settlement where recent immigrants could receive services like healthcare and language classes. Alice ended up treating many of the members of the community for injuries and conditions they sustained on the job.

She credited her time at Hull-House as one of the main reasons she started researching what were then called industrial diseases. So, she turned her medical and scientific training to the issue of making these workplaces safer, starting with her own. In 1905, she published a paper on the transmission of Scarlet Fever and similar diseases in hospital settings and made some findings that are especially salient today.

She had a group of patients with Scarlet Fever cough, cry and breathe over a set of petri dishes, and then incubated the samples to see if Streptococcus pyogenes, the microbe that caused Scarlet Fever, was present. Which it absolutely was. And she found that the best way to block it was to simply cover the mouth and the nose.

Because the vector for the disease seemed to be saliva and respiratory droplets. So, she recommended that surgeons always wear masks when performing surgery because you could have Scarlet Fever but have yet to show symptoms. This was a really important move in occupational safety for hospital workers but the results held true for any disease where respiratory droplets could be a vector.

Making these findings monumental in public health. Among other research, her work is why mask-wearing caught on to reduce the spread of disease. First during the 1918 Spanish Flu, and more recently with things like SARS, MERS and Covid-19.

While some of her early work was studying respiratory diseases, Alice would really make a name for herself when it came to industrial toxins. She was hired to investigate lead first by the State of Illinois and later by the US Department of Labour. Because lead was cheap and really easy to work with it was used in just about everything.

Like pipes, foil and paint. And the thing is, people already knew lead was toxic, they just didn't understand how. We now believe that lead is poisonous because the body mistakes it for calcium, which the body uses for bones and teeth, and in lots of cell-signalling pathways controlling muscle and neuron function. This means that lead concentrates in bones and teeth, in nerves and in the brain. And when lead deposits in bone rather than immediately gumming up the works in you brain and muscles, then you've got a super fun lead reserve in your body that can be slowly released long after exposure. 

So at the time Alice Hamilton was beginning her research you'd see a wide variety of symptoms in folks who worked with lead, and the onset and development of those symptoms didn't always coincide with exposure, which made it difficult to pin down lead as the source of these illnesses, and the owners of these factories were perfectly happy with that, blaming symptoms on alcohol use or poor hygiene. 

But doctor Hamilton proved them both wrong and very liable. In order to gather her data, she basically had to become an investigative reporter. She'd slip into factories without the owners' permission, because the owners regularly lied about how much lead they were using and how they used it. She'd also take factory workers and union leaders out for beers, so they could speak freely, and had workers sneak her samples of materials so she could test them for lead. And she discovered over 70 industrial processes through which workers were being poisoned and killed leading to major safety overhauls in the lead industry, as well as the replacement of lead, in stuff like paint and foil.

Her work made her the expert in occupational health, so when Harveard began their industrial hygiene program; they hired her on as an assistant professor. She never got tenure, you can maybe guess why, but she did negotiate for half of every year off, to continue her field work. And it's because of her efforts that the United States has organizations like OSHA and NIOSH which create guidelines for workplace safety and continue to research workplace health hazards.

So thanks to Alice Hamilton's ingenious scientific mind, and unparalleled awesomeness, the world is a much safer place. 

Without great minds like these, the world would be a darker, sometimes more dangerous place. And that's true of the scientists and engineers working today too. So to all the researchers of the past, and all the ones still doing work today, thank you.

If you want to keep learning about scientists and discoveries like these, you can watch our episode about five researchers nobody believed, who were actually right. And as always, thanks for watching this episode too.

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