Start-Up Biochemistry Bonanza - Superhumans?
Darren Meade
December 18, 2007
Independent reports show that a team of 15 scientists, at Case Western Reserve University have created mice that show capabilities, "far beyond those of mortal mice." It all results from a seemingly minor genetic alteration. Most amazingly, this may be equally applicable to humans, since we have the very same gene. Essentially, the modified gene turns mice into the equivalent of world-class athletes.
The mice have phenomenal endurance. It's comparable to a person cycling up a mountainside for five hours without rest. A supermouse eats nearly two-thirds more food than an ordinary mouse, yet it does not put on excess fat. It even lives longer and is sexually active well into old age, far beyond normal mice.
The mice now exist in a colony of 500. They were created by modifying a single metabolic gene.
Biochemist Richard Hanson of Case Western compares these mice to Lance Armstrong, whom some have called the greatest cyclist ever. Armstrong won the Tour de France seven consecutive times from 1999-2005.
The gene is involved in the metabolism of glucose (a basic sugar and fuel source for cells), and it tunes up the body's use of fat for energy production. On the other hand, there is no aggregation of lactic acid, a problem that challenges us mere mortals in strenuous exercise.
Commented Professor Hanson:
"They are not eating or drinking and yet they can run for four or five hours. They are 10 times more active than ordinary mice in their home cage. They also live longer -- up to 3 years of age -- and are reproductively active for almost three years. In short, they are remarkable animals. On the downside, they eat twice as much as control mice, but they are half the weight, and are very aggressive. Why this is the case, we are not really sure."
The results of four years of research have just been published in the Journal of Biological Chemistry.
Dr. Hanson described human applications as follows:
"We humans have exactly the same gene. But this is not something that you'd do to a human. It's completely wrong. We do not think that this mouse model is an appropriate model for human gene therapy. It is currently not possible to introduce genes into the skeletal muscles of humans, and it would not be ethical to even try."
Nevertheless, he acknowledges that a drug could be developed to stimulate existing genes to simulate the effects of the modified gene. He also admitted that such drugs would have valid uses with disorders such as cystic fibrosis, even as they would surely find tremendous pressure for use in athletic competitions.
The aim of the research has been to gain a greater understanding of the PEPCK-C enzyme, found in the liver and kidneys. As a result of the genetic modification, the supermice have up to 100 times the amount of enzyme in muscles compared with ordinary mice.
Most intriguing about this is the possibility that a single gene can have such radical effects. A startup company that isolates such a gene's effects and patents them could have, very quickly, a valuable asset. "I consider such genetic analysis a promising field for startups and am watching closely."
Of course, the behavioral changes associated with this are significant -- and might prevent this from ever being safely applied to humans. More likely, this is just the first discovery in a future filled with subtlety. I expect that additional variants of this gene will either be discovered in nature or synthesized (as I have reported, Nobel Laureate J. Craig Venter's group is poised to create the world's first synthetic life form next year). It should be possible to tailor these variants to retain at least some of the benefits of the current one, but without the behavioral consequences.
In my view, the professor is naive to think that such knowledge will never be deployed. Every scientific advance has eventually been used, whether for good or ill.
It's also important to recognize that such genetic improvements, assuming they are validated through years of study, may not be limited to future mammals, including humans. The reason is that viruses can be and have already been genetically engineered to serve as carriers for the delivery of new genes to target cells. (That's what viruses do, though for less beneficent purposes.)
True, the mouse experiments have shown serious side effects on personality that are not yet fully understood, and others may well be discovered as the research is applied to humans. But that won't stop future experiments, especially when the potential benefits are so high. (Though not addressed in the story, it's probable that the supermice will have far less risk of diabetes than ordinary mice. For people with serious risk of type 2 diabetes, or even full-blown cases, the temptation to do something like this could be high.)
In theory, a virus could be made to deliver the variant metabolic gene to target cells in a child or even an adult person. Putting the ethical and safety issues aside -- and they are considerable -- this soon will be possible. It's just a new application of existing technology.
Once the supermice are better understood through several full cycles of life and a few other mammals show similar benefits, I fully expect some regime to begin using this on at least some of its citizens. (Former Eastern Bloc countries, notably East Germany, showed a willingness to aggressively drug their athletes to win contests. That's now illegal and traceable. But I wonder how this could be controlled, especially if the variant gene is found to naturally occur in some people.)
Mark my words, within five years, a similar intelligence-boosting gene or set of genes will also be discovered. Then the pressure for genetic engineering of people may become irresistible. Some society will do it, and then others will feel ever-increasing pressure to participate or else be left behind.
Welcome to the brave new world of genetic engineering. My firm Kairos-Meade handles business development for many such break-throughs. We will continue to share what we see emerging in the marketplace.
The mice have phenomenal endurance. It's comparable to a person cycling up a mountainside for five hours without rest. A supermouse eats nearly two-thirds more food than an ordinary mouse, yet it does not put on excess fat. It even lives longer and is sexually active well into old age, far beyond normal mice.
The mice now exist in a colony of 500. They were created by modifying a single metabolic gene.
Biochemist Richard Hanson of Case Western compares these mice to Lance Armstrong, whom some have called the greatest cyclist ever. Armstrong won the Tour de France seven consecutive times from 1999-2005.
The gene is involved in the metabolism of glucose (a basic sugar and fuel source for cells), and it tunes up the body's use of fat for energy production. On the other hand, there is no aggregation of lactic acid, a problem that challenges us mere mortals in strenuous exercise.
Commented Professor Hanson:
"They are not eating or drinking and yet they can run for four or five hours. They are 10 times more active than ordinary mice in their home cage. They also live longer -- up to 3 years of age -- and are reproductively active for almost three years. In short, they are remarkable animals. On the downside, they eat twice as much as control mice, but they are half the weight, and are very aggressive. Why this is the case, we are not really sure."
The results of four years of research have just been published in the Journal of Biological Chemistry.
Dr. Hanson described human applications as follows:
"We humans have exactly the same gene. But this is not something that you'd do to a human. It's completely wrong. We do not think that this mouse model is an appropriate model for human gene therapy. It is currently not possible to introduce genes into the skeletal muscles of humans, and it would not be ethical to even try."
Nevertheless, he acknowledges that a drug could be developed to stimulate existing genes to simulate the effects of the modified gene. He also admitted that such drugs would have valid uses with disorders such as cystic fibrosis, even as they would surely find tremendous pressure for use in athletic competitions.
The aim of the research has been to gain a greater understanding of the PEPCK-C enzyme, found in the liver and kidneys. As a result of the genetic modification, the supermice have up to 100 times the amount of enzyme in muscles compared with ordinary mice.
Most intriguing about this is the possibility that a single gene can have such radical effects. A startup company that isolates such a gene's effects and patents them could have, very quickly, a valuable asset. "I consider such genetic analysis a promising field for startups and am watching closely."
Of course, the behavioral changes associated with this are significant -- and might prevent this from ever being safely applied to humans. More likely, this is just the first discovery in a future filled with subtlety. I expect that additional variants of this gene will either be discovered in nature or synthesized (as I have reported, Nobel Laureate J. Craig Venter's group is poised to create the world's first synthetic life form next year). It should be possible to tailor these variants to retain at least some of the benefits of the current one, but without the behavioral consequences.
In my view, the professor is naive to think that such knowledge will never be deployed. Every scientific advance has eventually been used, whether for good or ill.
It's also important to recognize that such genetic improvements, assuming they are validated through years of study, may not be limited to future mammals, including humans. The reason is that viruses can be and have already been genetically engineered to serve as carriers for the delivery of new genes to target cells. (That's what viruses do, though for less beneficent purposes.)
True, the mouse experiments have shown serious side effects on personality that are not yet fully understood, and others may well be discovered as the research is applied to humans. But that won't stop future experiments, especially when the potential benefits are so high. (Though not addressed in the story, it's probable that the supermice will have far less risk of diabetes than ordinary mice. For people with serious risk of type 2 diabetes, or even full-blown cases, the temptation to do something like this could be high.)
In theory, a virus could be made to deliver the variant metabolic gene to target cells in a child or even an adult person. Putting the ethical and safety issues aside -- and they are considerable -- this soon will be possible. It's just a new application of existing technology.
Once the supermice are better understood through several full cycles of life and a few other mammals show similar benefits, I fully expect some regime to begin using this on at least some of its citizens. (Former Eastern Bloc countries, notably East Germany, showed a willingness to aggressively drug their athletes to win contests. That's now illegal and traceable. But I wonder how this could be controlled, especially if the variant gene is found to naturally occur in some people.)
Mark my words, within five years, a similar intelligence-boosting gene or set of genes will also be discovered. Then the pressure for genetic engineering of people may become irresistible. Some society will do it, and then others will feel ever-increasing pressure to participate or else be left behind.
Welcome to the brave new world of genetic engineering. My firm Kairos-Meade handles business development for many such break-throughs. We will continue to share what we see emerging in the marketplace.
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