When did science first spark your interest?

Question: When did science spark your interest?

Vest: Well you’ll hear a similar story from many people my age, I suspect. I had a very early interest in science and sort of things physical. And frankly a lot of it came from the fact that at the end of World War II, there was suddenly on the market all of this amazing army surplus equipment – microphones, and head phones, and radio components. And very early on I got interested in playing with things like that; with working with them with my hands; reading all the typical magazines of Popular Mechanics and Popular Science and so forth. The interesting thing however is that I never really developed any affection at all for mathematics until somewhat later. And so it really wasn’t until about the time that I was in high school and college that I started liking the more abstract-analytical part of science. But a lot of it went really back to playing with surplus equipment. I have to tell you one other story because it’s a little amusing. One of my schoolmates in grade school . . . One of my schoolmate’s father was commander of the local state police post. And one of the things he had to do was raid places that were using slot machines. And he’d have to smash the front of the slot machine, and then his son and I got to tear it apart and get all the relays and components out of it. So I had a lot of fun like that – building model airplanes, all the usual things.I studied mechanical engineering as an undergraduate at West Virginia University. I actually lived at home and went to school to save money. And immediately upon graduation I was married and we moved to Ann Arbor, and I started graduate school at the University of Michigan. And after that for almost 20 years was a very straightforward kind of academic experience and career. I did my thesis work under a quite extraordinary professor from Turkey named Veda Arpiche, and we worked in what I would really call “applied science” today. We worked on something called Hydrodynamic Stability Theory. But it was a lot of work in fluid mechanics, thermodynamics, heat transfer – which at that time were very exciting fields because they had advanced quite dramatically an association with the . . . with the space program. But I worked in a more sort of theoretical part of that. Then when I graduated I ended up having several opportunities to join good faculties around the country, but I ended up staying at the University of Michigan. And when I did that I decided well I should do something really different. The last thing I wanted to do was stay on and continue the kind of work my thesis advisor did. So at that time the field of holography – three dimensional photography, if you will, based on the use of then very new lasers – was being developed largely at Michigan because in its modern form it was really invented by two faculty members there – Emmitt Leath and ___________. So I decided to go over and start working in their laboratory which was an entirely different field populated by physicists, and electrical engineers, and optics experts. I was the only mechanical engineer. And I got very interested in how this technique of forming these amazing three dimensional images of things could be used to measure properties of importance in the kind of engineering I did. So together with my graduate students, we developed a number of techniques for taking these sort of qualitative images and making them quantitative measurement tools; and in particular became the nth group . . . Or “N” is a very large number to sort of independently discover the principles of computer tomography, which most people know from medical applications getting three dimensional measurements such as look inside of the brain structure and so forth. We did this for things like wind tunnels, and flames, and chemical experiments. And so I did a lot of things all around the theme of taking classical engineering problems and applying this sort of radical new measurement technique to it and moving that technique from something that was qualitative to something that could make quantitative measurements. That sort of in a nutshell is what I did. I planned at that point nothing other than a straightforward academic career because I loved teaching. That’s really why I became a professor even more than the research side. I love teaching, working with my graduate students, doing research, and figured I’d probably do that ‘til I retired. But things turned a corner later. Recorded on: 12/5/07

 

There was lots of surplus WW II equipment lying around.

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Yale scientists restore brain function to 32 clinically dead pigs

Researchers hope the technology will further our understanding of the brain, but lawmakers may not be ready for the ethical challenges.

Still from John Stephenson's 1999 rendition of Animal Farm.
Surprising Science
  • Researchers at the Yale School of Medicine successfully restored some functions to pig brains that had been dead for hours.
  • They hope the technology will advance our understanding of the brain, potentially developing new treatments for debilitating diseases and disorders.
  • The research raises many ethical questions and puts to the test our current understanding of death.

The image of an undead brain coming back to live again is the stuff of science fiction. Not just any science fiction, specifically B-grade sci fi. What instantly springs to mind is the black-and-white horrors of films like Fiend Without a Face. Bad acting. Plastic monstrosities. Visible strings. And a spinal cord that, for some reason, is also a tentacle?

But like any good science fiction, it's only a matter of time before some manner of it seeps into our reality. This week's Nature published the findings of researchers who managed to restore function to pigs' brains that were clinically dead. At least, what we once thought of as dead.

What's dead may never die, it seems

The researchers did not hail from House Greyjoy — "What is dead may never die" — but came largely from the Yale School of Medicine. They connected 32 pig brains to a system called BrainEx. BrainEx is an artificial perfusion system — that is, a system that takes over the functions normally regulated by the organ. The pigs had been killed four hours earlier at a U.S. Department of Agriculture slaughterhouse; their brains completely removed from the skulls.

BrainEx pumped an experiment solution into the brain that essentially mimic blood flow. It brought oxygen and nutrients to the tissues, giving brain cells the resources to begin many normal functions. The cells began consuming and metabolizing sugars. The brains' immune systems kicked in. Neuron samples could carry an electrical signal. Some brain cells even responded to drugs.

The researchers have managed to keep some brains alive for up to 36 hours, and currently do not know if BrainEx can have sustained the brains longer. "It is conceivable we are just preventing the inevitable, and the brain won't be able to recover," said Nenad Sestan, Yale neuroscientist and the lead researcher.

As a control, other brains received either a fake solution or no solution at all. None revived brain activity and deteriorated as normal.

The researchers hope the technology can enhance our ability to study the brain and its cellular functions. One of the main avenues of such studies would be brain disorders and diseases. This could point the way to developing new of treatments for the likes of brain injuries, Alzheimer's, Huntington's, and neurodegenerative conditions.

"This is an extraordinary and very promising breakthrough for neuroscience. It immediately offers a much better model for studying the human brain, which is extraordinarily important, given the vast amount of human suffering from diseases of the mind [and] brain," Nita Farahany, the bioethicists at the Duke University School of Law who wrote the study's commentary, told National Geographic.

An ethical gray matter

Before anyone gets an Island of Dr. Moreau vibe, it's worth noting that the brains did not approach neural activity anywhere near consciousness.

The BrainEx solution contained chemicals that prevented neurons from firing. To be extra cautious, the researchers also monitored the brains for any such activity and were prepared to administer an anesthetic should they have seen signs of consciousness.

Even so, the research signals a massive debate to come regarding medical ethics and our definition of death.

Most countries define death, clinically speaking, as the irreversible loss of brain or circulatory function. This definition was already at odds with some folk- and value-centric understandings, but where do we go if it becomes possible to reverse clinical death with artificial perfusion?

"This is wild," Jonathan Moreno, a bioethicist at the University of Pennsylvania, told the New York Times. "If ever there was an issue that merited big public deliberation on the ethics of science and medicine, this is one."

One possible consequence involves organ donations. Some European countries require emergency responders to use a process that preserves organs when they cannot resuscitate a person. They continue to pump blood throughout the body, but use a "thoracic aortic occlusion balloon" to prevent that blood from reaching the brain.

The system is already controversial because it raises concerns about what caused the patient's death. But what happens when brain death becomes readily reversible? Stuart Younger, a bioethicist at Case Western Reserve University, told Nature that if BrainEx were to become widely available, it could shrink the pool of eligible donors.

"There's a potential conflict here between the interests of potential donors — who might not even be donors — and people who are waiting for organs," he said.

It will be a while before such experiments go anywhere near human subjects. A more immediate ethical question relates to how such experiments harm animal subjects.

Ethical review boards evaluate research protocols and can reject any that causes undue pain, suffering, or distress. Since dead animals feel no pain, suffer no trauma, they are typically approved as subjects. But how do such boards make a judgement regarding the suffering of a "cellularly active" brain? The distress of a partially alive brain?

The dilemma is unprecedented.

Setting new boundaries

Another science fiction story that comes to mind when discussing this story is, of course, Frankenstein. As Farahany told National Geographic: "It is definitely has [sic] a good science-fiction element to it, and it is restoring cellular function where we previously thought impossible. But to have Frankenstein, you need some degree of consciousness, some 'there' there. [The researchers] did not recover any form of consciousness in this study, and it is still unclear if we ever could. But we are one step closer to that possibility."

She's right. The researchers undertook their research for the betterment of humanity, and we may one day reap some unimaginable medical benefits from it. The ethical questions, however, remain as unsettling as the stories they remind us of.

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