Throughout the course, I will refer back to a handful of core examples that illustrate how diverse the scientific enterprise can be. I'll also use these examples to explain the characteristics that unify all scientific activity. So someone who spends a lot of time in nature, when I think about science, I don't immediately turn to laboratory or the stars, but what first comes to mind for me are the intricacies of forests, oceans, and deserts. So I'm going to start by describing what's arguably the greatest scientific achievement in biology: Evolutionary theory. When you went to work or school this morning, did you take the time to really look around? I live in Philadelphia and while it doesn't exactly fit the stereotype of an idyllic natural setting, even in the city every corner is teeming with life. You'd probably walk by some relatively large animals like pigeons and squirrels, maybe even a woodchuck, but if you stop to take a peek under some bushes or behind a dumpster, you'll probably spot some smaller mammals like mice and rats. Throughout the city, there are heaps of insects including cockroaches and bed bugs, which both seemed to survive our greatest attempts at eradication, and you'll also notice the trees they've coverings of moss and lichens. In darker corners of the city, we'll probably find spores, molds, and fungus. If you had a powerful microscope you'd see that billions of bacteria are in the soil of our parks, our buildings, and trolleys, and trains. Bacteria, in fact, are everywhere. On the table you're sitting at, on the computer you're watching this video on, on your skin and as you already now know, inside your body. There are a lot of questions we can ask about the diversity of life that permeates both our forests and our cities. How did the species get here in the first place and despite their diversity, why do they have so much in common? These questions are answered by evolutionary biology. I'm lucky to work in the Galapagos archipelago, which is located off the coast of mainland Ecuador in South America. This is one of the best places to study the phenomenon of adaptation. These islands were never attached to the mainland. When they first formed from volcanic eruptions millions of years ago, the islands were devoid of life. So every species that now calls them home had to swim, fly, or float there. These living things then adapted to the harsh environment where food and water were and continue to be scarce. The Galapagos giant tortoise, one of the last remaining species of giant tortoises on the planet, possesses one of the most striking adaptations in the island chain. Giant tortoises are land grazers, much like sheep or goats in North America, so there survival in the Galapagos environment depends on their ability to gain access to vegetation. On some of the islands where lush vegetation is available on or near the ground, tortoises with dome-shaped shells can easily access food. But some of the islands are extremely dry and vegetation is only available above the ground. On these islands, tortoise's shells take the shape of a horse's saddle and are aptly-named saddleback tortoises. This saddle shape allows these tortoises to reach their neck high up to eat the only available vegetation. Biologists would say that the saddleback tortoises are well adapted to life on dry islands, while the dome tortoises are well adapted to life on the lusher islands. This phenomenon, good fit between organisms and their environment, has been known all the way back to Aristotle. But since tortoises can't change their shell shapes, what explains that this adaptation? In fact, it was in the Galapagos archipelago that the naturalist Charles Darwin gathered some of the most important insights into the mechanisms by which populations of organisms adapt to their environments over generations. Darwin called this mechanism natural selection. We could do a whole course on evolution but, in brief, here's how it works. The key is to first take notice of subtle variations over drastic ones. Even though all of these tortoises are dome-shaped, each one is a little different. We can see these differences if we look at the V-shaped area of their shells; the two scales at the spot where the head sticks out. Some of these tortoises have their neck scales pointing forwards or downwards, but other tortoises have these scales pointed a little bit upwards. These individuals can reach their necks just a bit higher than their cousins with neck scales pointing forwards or downwards. When food on the ground is scarce, if a tortoise can reach just a little higher, it can get more food than the others. More food usually means more offspring and these offspring inherit the upturned shell trait. Then very slowly over many generations, there will be more and more tortoises with upturn shells on the driest islands. Eventually, after many generations, tortoises that live in these dry environments end up looking like the saddleback tortoises we see today. It's not just tortoises. Darwin and many biologists that came after him have also studied Galapagos finches to better understand adaptation. Like the tortoises, these 17 species of finch have adapted to life on different islands by specializing in obtaining food in different ways. Some have big beaks that can crack larger nuts and others have small narrow beaks better at handling smaller seeds. But their ancestors were all the same species, a species that likely flew over to the island chain thousands of years ago. So their beak shapes are largely the result of natural selection, helping populations to cope with different sources of food and again, natural selection work with small differences in body and beak shape. It's very hard to see these small differences what biologists call "variation" when we're in the field. But generations of scientists have brought samples of finches back to museums like this one so that they can be studied. Most studies of adaptation have to infer how natural selection operated since we can't go back and replay the past, but there are some important exceptions to this, and one of them happened in Galapagos. There, Peter and Rosemary Grant studied the medium ground finch on Daphne Major Island for 40 years. During that time, they were able to follow each individual bird and its offspring, observing how small differences in beak size made big differences for individual finches in years of drought. They found that in extreme drought when the only food that was available were hard woody tribulus seeds, the birds with larger beaks did better and pass these larger big traits to their offspring. Now you might be wondering, how practical is it to do a study like the one conducted by the Grants, one that lasts over 40 years and involves tagging every single animal in an entire island. The answer I'm sorry to say is it's not very practical. It's time-consuming and expensive and few areas of the world are as suited to such study as Daphne Major. It's a very small and isolated island even by the standards of the Galapagos. But there are other ways we can study natural selection. We can also study it in the laboratory which Professor Mia Levine is doing at Penn. My lab uses the model fruit fly of the genus Drosophila to conduct our evolutiogenic studies for a variety of reasons. So first, we can do experiments in the lab with this fruit fly. It lives in a tiny vial, it has a very short generation time, and we can pull from the 100 years of genetics that fruit flies have been huge contributors to and use those tools to ask actually evolutionary questions. There's also the genome sequences of hundreds of Drosophila species that we can leverage to discover those signatures of very recent adaptation or very recent evolution. My lab is very interested in the genes that make proteins that glom on to DNA in our cells. So we focus specifically on the subset of the 14,000 genes that Drosophila melanogaster, the model fruit fly in code, specifically looking at those genes that make proteins that do this important function. Once we've identified genes that change very rapidly between closely-related species, we use genetic engineering, specifically CRISPR-Cas9 mediated transgenesis, where we put foreign pieces of DNA back into that model fruit fly and ask what happens? So while a true molecular geneticist will knock out a gene or change some portion of that gene and ask what breaks in that organism in order to understand what that gene does, what my lab does instead is we take versions of that gene from closely-related species, put it back into a Drosophila melanogaster and ask what breaks. We think that what breaks when we put the wrong species version of that gene into our model organism, that tells us what's the biology that evolution has shaped in the past 500,000 to two million years of evolution. We are specifically interested in genes that encode proteins that glom on to the DNA. These proteins perform really important function. Function that you think shouldn't change between Drosophila and humans, let alone between two very closely related Drosophila species. One of our projects is understanding specifically why proteins that ensure our chromosome ends, maintain their integrity. Why should proteins like that change so rapidly between closely-related species? Now we can't do these gene swaps and simply look at the fly and ask, does its wing change or does its eye change or does it move differently? The phenotypes we're interested are ultimately phenotypes that we need to look inside the nuclei of this organism to detect. So we do that by not just putting the wrong species version of a gene into Drosophila melanogaster and seeing what breaks, but we actually put a special little tag as we call it on the end of the gene that allows us using antibodies and fluorescence microscopy to actually visualize where these wrong species versions of those proteins go inside the nucleus of this particular species. We then can infer the type of biology that has changed over these very short stretches of evolutionary time. We've now talked a lot about adaptation and natural selection, how it can be observed and how it can be studied. We've seen that the study of adaptation often begins in the field with careful observations of organisms in their environment. But when scientists need to get a bit more precise, they can take collections back to the laboratories for more careful measurement and analysis. Laboratory experiments also allow for direct manipulation, giving scientists a greater ability to control certain variables in the system. This allows them to pinpoint the effects of one variable from another. The most reliable information comes from the integration of different research methods. This we will see as equality that ties all of our core examples of science together.