Prime Time Replay:
Dr. James Gusella
on Research into Genetic Diseases
MsgId: chat(5)
Date: Wed Sep 25 21:59:34 EDT 1996
From: moderator At: 206.80.176.58
Hi, this is Madeleine Lebwohl, the moderator for Breakthrough Medicine. Tonight Dr. James Gusella, director of the molecular neurogenetics unit at Massachusetts General Hospital will be speaking about his research. Please e-mail any questions you would like to ask him to mlebwohl@unidial.com. Dr. Gusella, welcome!Dr. Gusella has recently received funding from the Dysautonomia Foundation to find the gene that cause the disease. Dysautonomia affects the autonomic and sensory nervous system. It is inherited, and at present there is no cure.
The importance of genetic research can be readily seen in the ripple effect that each new additional bit of information gives researchers. The same chromosome that holds the defective gene that cause Dysautonomia is also thought to cause torsion distonia and tuburous sclerosis. Each breakthru in scientific research gives hope to people who suffer from these genetic diseases.
The Dyautonomia Foundation is privately funded, but for research to continue Dr. Gusella is hoping that N.I.H. money will come through.
MsgId: chat(11)
Date: Wed Sep 25 22:19:47 EDT 1996
From: moderator At: 206.80.176.58
Hello, Dr. Gusella!
MsgId: chat(12)
Date: Wed Sep 25 22:20:33 EDT 1996
From: moderator At: 206.80.176.58
I've given a brief background of your work with the Dyautonomia Foundation, but would you like to add anything?
MsgId: chat(14)
Date: Wed Sep 25 22:24:03 EDT 1996
From: gusella At: 152.163.231.183
Just that my group works on a wide variety of genetic disorders, primarily affecting the nervous system in addition to dysautonomia.
MsgId: chat(15)
Date: Wed Sep 25 22:24:27 EDT 1996
From: moderator At: 206.80.176.58
Dr. Gusella, would you like to tell the audience anything pertinent to your research on Dysautonomia, or would you like to discuss the other work your lab does, such as the landmark discovery you made concerning the gene for Huntington's disease?
MsgId: chat(16)
Date: Wed Sep 25 22:28:48 EDT 1996
From: gusella At: 152.163.231.155
My group works on a wide variety of genetic disorders with a four step strategy: 1) Map the location of a genetic defect on a chromosome by tracing it through families; 2) isolate the gene bassed on this chromosomal position; 3) characterize how the defective gene causes the disease symptoms and 4) try to base a treatment on the knowledge gained. We work on Alzheimer disease, Huntington's disease, Parkinson disease, neurofibromatosis and several other disorders. I'd be happy to answer questions about any of them or the strategy in general.
MsgId: chat(17)
Date: Wed Sep 25 22:28:55 EDT 1996
From: moderator At: 206.80.176.58
I'm sure people in the audience would also be interested to hear about your research that searchs for genes responsible for the more complex genetic disorders that affect behavior, such as schizophrenia and panic disorder. Let's talk about the families that come into your lab, hoping to find a cure for their disorders. Are you seeing a people who believe that the research will help them in an immediate way?
MsgId: chat(20)
Date: Wed Sep 25 22:33:31 EDT 1996
From: gusella At: 152.163.231.183
The work on the more complex disorders requires a slightly different strategy since they are not easily traced in single families. Instead we must compare the chromosomal regions shared by affected relatives to find the chromosomal locations of risk factors and predisipositions to set us on the path to isolating and characterizing them. Most of the work on complex disorders is in that early searching stage. Since the searching is easier in some of the disorders with simpl inheritance, like Huntington's disease, those disease genes hav already been found and we are now trying to figure out how they work.
MsgId: chat(21)
Date: Wed Sep 25 22:36:09 EDT 1996
From: moderator At: 206.80.176.58
And what strategies do you follow to figure that out?
MsgId: chat(22)
Date: Wed Sep 25 22:36:36 EDT 1996
From: gusella At: 152.163.231.165
Many of the people with these disorders hope for an immediate treatment but most are realistic enough to know that these things take lots of time and lots of effort. The disorders that they know only too well are often so devastating that the research offers th only long-term hope for them and they are our biggest backers. Th immediate result of most of our work is better diagnosis rather than treatment, but we hope that will come with more work.To figure out how a disease gene works means deciphering its normal function and what differences result when the protein made from the gene is defective. This means comparing normal individuals with those with the disorder and then analyzing things in fine detail in a manipulable model system: tissue culture cells, mice, Fruit flies or other organisms.
MsgId: chat(24)
Date: Wed Sep 25 22:41:40 EDT 1996
From: moderator At: 206.80.176.58
I understand you have used strains of mice to track genetic defects?
MsgId: chat(25)
Date: Wed Sep 25 22:44:56 EDT 1996
From: gusella At: 152.163.231.155
There are sometimes mice that have mutations in the same gene that causes a human disease, but most of the time when you find a human disease gene it is necessary to manipulate the mouse's genes to give it the same mutation and to then see whether the mouse shows symptoms similar to those in Man. If so, you then have an experimental model of the human disease that you can study with greater ease and in greater detail than is possible with people. These mice also can be used as a first-line test of treatments before they are attempted with patients.
MsgId: chat(26)
Date: Wed Sep 25 22:45:19 EDT 1996
From: moderator At: 206.80.176.58
Let's discuss the way your research fits into the bigger picture of mapping the human chromosome.
MsgId: chat(27)
Date: Wed Sep 25 22:50:10 EDT 1996
From: gusella At: 152.163.231.155
The genes we are most interested in are those that cause disease. However, there is a major project underway to catalogue and sequence all human genes and that work provides an infrastructure that is very useful to us and other interested in particular types of human genes. Ultimately, when all the genes are catalogued, the kinds of variations that we look at along with normal variations in the genes will be essential to understanding how they work to make a human, an understanding that is not achieved simply by having the gene's sequence.
MsgId: chat(28)
Date: Wed Sep 25 22:53:16 EDT 1996
From: moderator At: 206.80.176.58
So understanding how diseases function are crucial to understanding what is happening when we are healthy?
MsgId: chat(29)
Date: Wed Sep 25 22:56:29 EDT 1996
From: gusella At: 152.163.231.155
Yes, if genes all operated the same way in all people we would all be like identical twins. It is the variations in the genes that cause all inherited differences between people and studying those differences can tell you things about how the genes do their jobs. The disease genes that we study can be viewed as simply an extreme on a spectrum of variation, most of which is in the normal range of function.
MsgId: chat(30)
Date: Wed Sep 25 23:00:41 EDT 1996
From: moderator At: 206.80.176.58
Do you have any thoughts on what pushes genes into their initial mutations, say when a disease first appears in the population?
MsgId: chat(31)
Date: Wed Sep 25 23:05:47 EDT 1996
From: Gusella At: 152.163.231.165
Mutations occur at random at a low frequency which can be increased by environmental mutagens. However, once a mutation occurs it is usually selected against because the individual with it is less fit. Sometimes, being a carrier of a mutation makes you more fit by helping with resistance to common infectious disorders and this causes the mutation to persist in the population although in these cases only the people with two copies of the disease gene suffer the genetic illness.
MsgId: chat(32)
Date: Wed Sep 25 23:06:04 EDT 1996
From: moderator At: 206.80.176.58
For the coming year, what will be your main interests?
MsgId: chat(34)
Date: Wed Sep 25 23:08:51 EDT 1996
From: Gusella At: 152.163.231.135
Our major goals for the coming year are to isolate the genes that cause familial dysautonomia and torsion dystonia, to create a true mouse model of Huntington's disease and to get the studies of complex disorders like Parkinson disease and schizophrenia well under way and moving to completion for mapping risk factors.
MsgId: chat(35)
Date: Wed Sep 25 23:14:25 EDT 1996
From: moderator At: 206.80.176.58
Dr. Gusella, thank you for talking to us tonight on Breakthru Medicine. Please tune in next week. Thank you again, Dr. Gusella, for your time.
MsgId: chat(36)
Date: Wed Sep 25 23:16:38 EDT 1996
From: Gusella At: 152.163.231.165
It was a pleasure. Thank you.
MsgId: chat(37)
Date: Wed Sep 25 23:17:04 EDT 1996
From: moderator At: 206.80.176.58
Thank you, and good night.
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