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ASU expert selects Darwin Day answers, naturally

ASU expert explains what Charles Darwin got right, wrong for Darwin Day.
February 11, 2018

Feb. 12 is Charles Darwin Day, a perfect time to catch up on what's evolving in paleoanthropology

It’s easy to watch the evening news and assume Homo sapiens is one of the most recalcitrant species on the planet. But humans are, surprisingly enough, one of the most cooperative species, and we evolved to be that way, according to one Arizona State University expert.   

Institute of Human Origins Director William Kimbel took time to share a few answers with ASU Now on the study of evolution, just in time for Charles Darwin Day on Feb. 12. 

Question: What do we get wrong about the term "natural selection"?

Answer: A lot of people have the idea that natural selection is a circular argument. If natural selection is the survival of the fittest, then the fittest survive and so the cause and the effect are related to one another. 

Darwin’s description of natural selection was not based on survival of the fittest; it was based on the idea that individuals who inherit characteristics that enable them to survive and reproduce in particular environments — where those traits are at an advantage — that these characteristics will increase in proportion to the traits that are less well-suited to solving these environmental problems, so it’s really about differential reproductive success.

Q: How has the study of evolution evolved since Charles Darwin? 

A: We know about the mechanism of inheritance, DNA and how it underpins the transmission of heritable characteristics from one generation to the next. That mechanism was unknown to Darwin and his contemporaries, and while they had an incorrect understanding of inheritance, it didn’t affect Darwin’s ability to put forward a valid theory. The mechanisms of inheritance were obvious for everyone to see through breeding, experiments and so forth.

But our record of human origins is vastly increased in quality and density over time compared to what Darwin knew, and so we inherit Darwin’s mantle as the guiding theoretical framework as our understanding of human origins.

We now have a rich database to consult on the details of that evolution and the causal prophecies: the why and the how and so forth that are responsible for how humans became such a dominant species on the planet.

Q: What did Darwin get wrong? 

A: He didn’t understand inheritance because he didn’t have access to a rich fossil [human] record. In "The Descent of Man," published in 1871, he describes an explanatory model for how humans became differentiated from the tree-dwelling apes.

He put down a model which became hugely influential in the field of human origins. It posited that human ancestors came down form the trees to the ground and adopted an upright posture on the ground, hands were freed from locomotor constraints and became able to be used instead for the manipulation of the environment principally through tool-making and that tool-making had a stimulating effect on intelligence as read through brain size. Tools also replaced the giant dagger, like canine teeth, which had commonly been thought to be used in defense.

He wrote it as though all the components of that model would have evolved more or less simultaneously.

What the fossil record tells us is that a lot of the pieces of that model don’t appear in the geological record at the same time, which means they can’t possibly be explained all at once with one encompassing model that endows our first ancestors … with all of those characteristics. 

So Darwin got far more right than he got wrong, and much of what he got wrong was simply because the answers that we now have were not available to him. 

Q: What should we be excited about in the field of paleoanthropology? 

A: All of it. I’m not being cute. 

There are numerous questions being pursued now from a variety of evolutionary perspectives on questions about how we became human. What were the causes of the divergence of our line from the line of the ancestor we share with the chimpanzee line? We know approximately when that happened, thanks to the molecular clock, based on the DNA differences.

And then there is the relationship between stone tools. The oldest stone tools have typically been associated with the rise of our own genus Homo about 2 million to 2.5 million years ago, but now we have very crude stone tools associated with fossils around 3.3 million to 3.4 million years ago.

There are new fossils being found in Africa that bear on the earliest stages of the rise of our own species. We now have the addition of genetic, DNA evidence into that story. 

One of our own scientists, Curtis Marean, works in South Africa on the Cape Coast, (which) has some of the earliest evidence, archeological evidence, for modern humans. We want to try to understand how modern human behavioral characteristics created advantages for populations that enabled them to spread across the continent and ultimately out of Africa and to populate the rest of the world as we’ve done. 

Q: Is Homo sapiens still evolving?

A: So the answer is yes, but it’s different. If you went back to Lucy’s time or the earliest Homo sapiens or any of the number of species in between, our evolution would look rather different. At some point in the past we started to evolve predominantly in terms of our culture rather than our physical features.

Make no mistake, our genetic evolution is still occurring. Much of our evolution, especially the fastest part of it, comes from our unusual ability to transmit information through technology from generation to generation. Our ability to transmit cultural information and to cooperate on a massive scale, those are fairly recent events in our evolution that can be taken from the most recent prehistoric periods right into the historic periods of our history. 

We have scientists here too as part of the Institute of Human Origins group who are investigating this with folks who are interested in the origins and the evolutionary advantages of large-scale cooperation in different types of societies today. They are comparing it to the work that the folks are doing on the great apes, looking for how or if they cooperate. From a large-scale perspective, a lot of the action late in our evolution has to do with the evolution of our culture and how we became the most cooperative species on the planet.

Top images courtesy of New York Public Library digital collections

Deanna Dent

Photographer , ASU News


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Cancer-fighting nanorobots seek and destroy tumors

February 12, 2018

ASU scientists have successfully programmed nanorobots to shrink tumors by cutting off their blood supply

Editor's note: This story is being highlighted in ASU Now's year in review. Read more top stories from 2018 here.

In a major advancement in nanomedicine, Arizona State University scientists, in collaboration with researchers from the National Center for Nanoscience and Technology (NCNST) of the Chinese Academy of Sciences, have successfully programmed nanorobots to shrink tumors by cutting off their blood supply.

“We have developed the first fully autonomous, DNA robotic system for a very precise drug design and targeted cancer therapy,” said Hao Yan, director of the ASU Biodesign Institute’s Center for Molecular Design and Biomimetics and the Milton Glick Professor in the School of Molecular Sciences.

“Moreover, this technology is a strategy that can be used for many types of cancer, since all solid tumor-feeding blood vessels are essentially the same,” Yan said.

The successful demonstration of the technology, the first-of-its-kind study in mammals utilizing breast-cancer, melanoma, ovarian and lung-cancer mouse models, was published in the journal Nature Biotechnology.

Seek and destroy

Yan is an expert in the field of DNA origami, which in the past two decades has developed atomic-scale manufacturing to build more and more complex structures.

The bricks to build their structures come from DNA, which can self-fold into all sorts of shapes and sizes — all at a scale 1,000 times smaller than the width of a human hair — in the hopes of one day revolutionizing computing, electronics and medicine.

That one day may be coming a bit faster than anticipated.

RELATED: 'DNA origami' is the shape of things to come for nanotechnology

Nanomedicine is a new branch of medicine that seeks to combine the promise of nanotechnology to open up entirely new avenues for treatments, such as making minuscule, molecule-sized nanoparticles to diagnose and treat difficult diseases, especially cancer.

Until now, the challenge of advancing nanomedicine has been difficult because scientists wanted to design, build and carefully control nanorobots to actively seek and destroy cancerous tumors — while not harming any healthy cells.

The international team of researchers overcame this problem by using a seemingly simple strategy to very selectively seek and starve out a tumor.

This work was initiated about five years ago. The NCNST researchers first wanted to specifically cut off tumor blood supply by inducing blood coagulation with high therapeutic efficacy and safety profiles in multiple solid tumors using DNA-based nanocarriers. Yan’s expertise has upgraded the nanomedicine design to be a fully programmable robotic system, able to perform its mission entirely on its own.

“These nanorobots can be programmed to transport molecular payloads and cause on-site tumor blood-supply blockages, which can lead to tissue death and shrink the tumor,” said Baoquan Ding, a professor at the NCNST in Beijing.

Video animation by Jason Drees, Arizona State University

Nanobots to the rescue

To perform their study, the scientists took advantage of a well-known mouse tumor model, where human cancer cells are injected into a mouse to induce aggressive tumor growth.

Once the tumor was growing, the nanorobots were deployed to come to the rescue.

Each nanorobot is made from a flat, rectangular DNA origami sheet, 90 nanometers by 60 nanometers in size. A key blood-clotting enzyme, called thrombin, is attached to the surface.

Thrombin can block tumor blood flow by clotting the blood within the vessels that feed tumor growth, causing a sort of tumor mini heart attack and leading to tumor tissue death.

First, an average of four thrombin molecules was attached to a flat DNA scaffold. Next, the flat sheet was folded in on itself like a sheet of paper into a circle to make a hollow tube.

They were injected with an IV into a mouse, then traveled through the bloodstream, homing in on the tumors.

The key to programming a nanorobot that attacks only a cancer cell was to include a special payload on its surface, called a DNA aptamer. The DNA aptamer could specifically target a protein, called nucleolin, that is made in high amounts only on the surface of tumor endothelial cells — and not found on the surface of healthy cells.

Once bound to the tumor blood vessel surface, the nanorobot was programmed, like the notorious Trojan horse, to deliver its unsuspecting drug cargo into the very heart of the tumor, exposing the thrombin.

The nanorobots worked fast, congregating in large numbers to quickly surround the tumor just hours after injection.

Safe and sound design

First and foremost, the team showed that the nanorobots were safe and effective in shrinking tumors.

“The nanorobot proved to be safe and immunologically inert for use in normal mice and, also in Bama miniature pigs, showing no detectable changes in normal blood coagulation or cell morphology,” said Yuliang Zhao, also a professor at NCNST and lead scientist of the international collaborative team.

Most importantly, there was no evidence of the nanorobots spreading into the brain where they could cause unwanted side effects, such as a stroke.

“The nanorobots are decidedly safe in the normal tissues of mice and large animals,” said Guangjun Nie, another professor at the NCNST and a key member of the collaborative team.

The treatment blocked tumor blood supply and generated tumor tissue damage within 24 hours while having no effect on healthy tissues. After attacking tumors, most of the nanorobots were cleared and degraded from the body after 24 hours.

By two days, there was evidence of advanced thrombosisLocal coagulation or clotting of the blood., and at three days, thrombi in all tumor vessels were observed.

The key is to trigger thrombin only when it is inside tumor blood vessels. Also, in the melanoma mouse model, three out of eight mice receiving the nanorobot therapy showed complete regression of the tumors. The median survival time more than doubled, extending from 20.5 to 45 days.

They also tried their system in a test of a primary mouse lung-cancer model, which mimics the human clinical course of lung-cancer patients. They showed shrinkage of tumor tissues after a two-week treatment.

Science of the very small goes big

For Yan, the important study milestone represents the end of the beginning for nanomedicine.

“The thrombin-delivery DNA nanorobot constitutes a major advance in the application of DNA nanotechnology for cancer therapy,” Yan said. “In a melanoma mouse model, the nanorobot not only affected the primary tumor but also prevented the formation of metastasis, showing promising therapeutic potential.”

Yan and his collaborators are now actively pursuing clinical partners to further develop this technology.

“I think we are much closer to real, practical medical applications of the technology,” Yan said. “Combinations of different rationally designed nanorobots carrying various agents may help to accomplish the ultimate goal of cancer research: the eradication of solid tumors and vascularized metastases. Furthermore, the current strategy may be developed as a drug-delivery platform for the treatment of other diseases by modification of the geometry of the nanostructures, the targeting groups and the loaded cargoes.”

This work was supported by grants from National Basic Research Plan of China (MoST Program 2016YFA0201601), the National Natural Science Foundation of China (31730032, 21222311, 21573051, 91127021, the National Distinguished Young Scientists program 31325010), Innovation Research Group of National Natural Science Foundation (11621505, 21721002), Beijing Municipal Science & Technology Commission (Z161100000116035, Z161100000116036), CAS Interdisciplinary Innovation Team, K. C. Wong Education Foundation and US National Institutes of Health Director’s Transformative Research Award (R01GM104960-01).

Top image: Cartoon graphic by Baoquan Ding and Hao Yan

Joe Caspermeyer

Manager (natural sciences) , Media Relations & Strategic Communications