Prime Time Replay:
Dr. Robert McCunney
on the Use of Biomarkers in Assessing
Environmental and Occupational Health
MsgId: *breakthrough(1)
Date: Wed Jun 4 10:39:50 EDT 1997
From: moderator At: 152.163.204.7
Good evening, and welcome to Breakthrough Medicine. I'm your moderator, Madeleine Lebwohl, and tonight I'll be speaking with Robert McCunney, M.D., M.P.H., director of the Environmental Medical Service at the Massachusetts Institute of Technology. He is also vice president of the American College of Occupational and Environmental Medicine. Hello, Dr. McCunney!
MsgId: *breakthrough(3)
Date: Wed Jun 4 21:00:57 EDT 1997
From: Dr_McCunney At: 152.163.213.9
Hi Madeline, nice to be here.
MsgId: *breakthrough(5)
Date: Wed Jun 4 21:06:21 EDT 1997
From: moderator At: 206.80.165.26
Dr. McCunney, let's begin by talking about a subject you recently presented at a conference in Charleston,South Carolina that was sponsored by the Department of Energy, and covered many aspects of the human genome, and how it relates to exposure with occupational and environmental hazards.
MsgId: *breakthrough(6)
Date: Wed Jun 4 21:08:38 EDT 1997
From: Dr_McCunney At: 206.80.165.26
The presentation I made in South Carolina related to clinical aspects of biomarkers and the human genome. The human genome refers to the essential genetic makeup of cells. Biomarkers, according to the National Research Council, refer to some sort of indicator of exposure to a hazard, be it a marker of an effect, disease, or susceptibility. Now, since most cancers are based at least in part on some genetic abberation, concern is raised on how certain aspects of the human genome can indicate early risk of cancer.Now, the major concern in occupational and environmental settings is whether exposure to a hazard will increase the risk of developing cancer. By studying the human genome we can theoretically uncover early signs of genetic damage that may indicate cancer later in life. In the occupational setting, where people may have contact with a variety of materials, some of which may be carcinogens, some of which may not be completely studied, concern may be raised about whether these substances can increase a persons risk of cancer. In work settings, there are three potential opportunities to use biomarkers to prevent cancer. First, at the time of employment or placement at a certain hazardous job, Second, in the course of certain work assignments, to determine whether work has affected the genome, and Three, in the context of a person with symptoms or a particular illness to determine whether an occupational or environmental hazard has caused the symptoms or the disease.
Beryllium, a very light metal with extraodinarilly high tensile strength, has wide application in the aeronautics and electronics industry. Its use at this point is limited to laboratory settings and highly controlled industrial settings. Exposure to this metal can cause a serious disabling lung disorder that can be fatal upon very limited exposure. The proper use of the human genome offers the potential, as yet unrealized, of predicting those people at higher risk of developing a lung disorder or lung cancer from working with beryllium.
MsgId: *breakthrough(12)
Date: Wed Jun 4 21:27:00 EDT 1997
From: moderator At: 206.80.165.26
So do people get tested while they work with this metal?
MsgId: *breakthrough(13)
Date: Wed Jun 4 21:28:11 EDT 1997
From: Dr_McCunney At: 206.80.165.26
The application of the human genome in the context of exposure to beryllium offers the potential to 1. Uncover those at risk, or 2. to show signs of early changes in the genome, secondary to beryllium.
MsgId: *breakthrough(14)
Date: Wed Jun 4 21:29:00 EDT 1997
From: moderator At: 206.80.165.26
Are there more common situations, more common materials, that people work with, which may cause genetic damage?
MsgId: *breakthrough(15)
Date: Wed Jun 4 21:31:07 EDT 1997
From: Dr_McCunney At: 206.80.165.26
At this point, beryllium is the only substance used in industry for which a certain genetic profile appears to be associated with an increased risk for disease. On the other hand, there is relatively strong scientific evidence that certain genotypes indicate an increased risk for lung cancer, often in the context of cigarette smoking. Whether certain genotypes indicate increased risks from other hazards, such as asbestos, arsenic, chrome, and other metals, remains to be seen.
MsgId: *breakthrough(16)
Date: Wed Jun 4 21:31:46 EDT 1997
From: moderator At: 206.80.165.26
Why did beryllium get worked on first?
MsgId: *breakthrough(17)
Date: Wed Jun 4 21:35:19 EDT 1997
From: Dr_McCunney At: 206.80.165.26
Madeleine, that's an excellent question. Beryllium was first studied for a number of reasons, Including the fact that berylliosis is an extremely rare disease, and 2, it is a disease with serious consequences, including death, and 3, in contrast to nearly every other occupational and environmental hazard that has been studied, risk of contracting berylliosis appears to be independent of the dose. In other words, just like the more alcohol one drinks, or the more cigarettes one smokes, one is more likely to have acute or chronic health problems, with beryllium, however, people have developed serious disease with trivial levels of exposure.For example, I am aware of an unfortunate woman who, a few years ago, developed such serious berylliosis, despite working as a secretary and not in the plant, that she needed a heart-lung transplant. Clearly, this example is an extroadinary exception, but it amplifies how medical scientist became curious how this disease would occur. This disease lead medical scientists to become curious about why some people would be at such a risk of this unfortunate disease. They then studied the genome of people with the illness, and found that upwards of 95% of those with the disease who were studied, and found that they had certain type of genetic makeup.
MsgId: *breakthrough(20)
Date: Wed Jun 4 21:39:09 EDT 1997
From: moderator At: 206.80.165.26
Are there other materials where you can be tested for damage to your genome?
MsgId: *breakthrough(21)
Date: Wed Jun 4 21:41:53 EDT 1997
From: Dr_McCunney At: 206.80.165.26
At this point, you can be tested for very few substances. Essentially, what they've done is they've studied groups of workers such as operating room personnel who may be exposed to a substance known as ethylene oxide, which is used in hospitals to sterilize surgical equipment. These workers when contrasted with people not exposed to ethylene oxide, often have higher rates of genetic damage.
MsgId: *breakthrough(23)
Date: Wed Jun 4 21:43:08 EDT 1997
From: moderator At: 206.80.165.26
When you say genetic damage, what do you mean exactly?
MsgId: *breakthrough(24)
Date: Wed Jun 4 21:46:05 EDT 1997
From: Dr_McCunney At: 206.80.165.26
There are a number of ways of assessing genetic damage from exposure to a hazard. None of these methods is perfect, and various scientific studies have used a range of parameters to assess genetic damage. For example, DNA adducts, are widely used in scientific investigations around the world to uncover some effect between exposure to a hazard and effect on the genes. The full benefit of using DNA adducts, however, because not everyone who has a particular kind of DNA adduct has the potential for developing cancer.
MsgId: *breakthrough(25)
Date: Wed Jun 4 21:46:41 EDT 1997
From: moderator At: 206.80.165.26
What is a DNA adduct?
MsgId: *breakthrough(26)
Date: Wed Jun 4 21:49:05 EDT 1997
From: Dr_McCunney At: 206.80.165.26
DNA adducts are formed when a hazard binds with the DNA. Its essentially a compound with the foreign substance and the DNA. There are, of course, DNA repair enzymes that are called into play to respond to these adducts. In addition, the location on the genome where the DNA adduct is may not be of clinical relevance, in essence, be a problem. So it may indicate merely a marker of exposure, and not risk of disease.
MsgId: *breakthrough(27)
Date: Wed Jun 4 21:50:21 EDT 1997
From: moderator At: 206.80.165.26
Can people use DNA adducts to apply for workmen's compensation?
MsgId: *breakthrough(28)
Date: Wed Jun 4 21:51:53 EDT 1997
From: Dr_McCunney At: 206.80.165.26
I wouldn't be surprised if science advances, and people can use DNA specific adducts to document exposure to a carcinogen. At this point I'm unaware of DNA adducts being used in that context. However, I would not be at all surprised if in the next ten years we read of such efforts.
MsgId: *breakthrough(29)
Date: Wed Jun 4 21:54:13 EDT 1997
From: moderator At: 206.80.165.26
Why is so much known about the effects of a rare material like beryllium but there is so much less for something really prevalent, like asbestos?
MsgId: *breakthrough(30)
Date: Wed Jun 4 21:54:52 EDT 1997
From: guest At: 153.35.119.228
How, then, is risk detected?
MsgId: *breakthrough(31)
Date: Wed Jun 4 21:55:49 EDT 1997
From: Dr_McCunney At: 206.80.165.26
People often come in to my office after having been exposed to a hazard such as asbestos, and wonder if that exposure would cause them to get cancer. People rarely ask if my risk will be increased. They already sense that. They want to know if they will get cancer. And it's in answering that question that I think the human genome offers real promise.In the future, many years down the road, most likely, through the detection of DNA damage from a carcinogen, there is the potential for developing DNA repair to prevent the cancer from occurring. This is the extroadinary science fiction promise, but who knows, the way science is developing, whether it is as far out in the future as I imagine.
In the future, many years down the road, most likely, through the detection of DNA damage from a carcinogen, there is the potential for developing DNA repair to prevent the cancer from occurring. This is the extroadinary science fiction promise, but who knows, the way science is developing, whether it is as far out in the future as I imagine.
To answer the question how risk is detected, to determine risk from exposure to a hazard two methods are used. 1. the results of animal investigation, and 2. The use of human epidemiology studies. The latter type of study carries the most weight, that is, when one group of people exposed to a hazard is contrasted with a similar group of people not exposed to the same hazard. Then the two groups are contrasted for risks of various diseases.
Then, scientists attempt to determine the risk of developing cancer associated with variable levels of exposure, just like one drink of beer is not going to cause cirrhosis, exposure to minimal amounts of a carcinogen is unlikely to cause cancer. So ultimately risk is determined by a full determination of human and animal studies with major emphasis being given to human studies.
MsgId: *breakthrough(36)
Date: Wed Jun 4 22:05:01 EDT 1997
From: moderator At: 206.80.165.26
When someone needs a job, are they someday going to consider these hazards more than they do now? Or are employers already considering selectively hiring on this basis?
MsgId: *breakthrough(37)
Date: Wed Jun 4 22:07:45 EDT 1997
From: Dr_McCunney At: 206.80.165.26
Clearly, genetic testing offers the potential for abuse by employers who want to discriminate in the hiring process, by insurance who either don't want to provide health insurance or who want to increase the cost, among others. As a result there are serious ethical concerns that ought to be properly addressed to insure the prevention of discrimination and the protection of private medical information. Moreover, whenever genetic testing is conducted, and at this point I would advise against it except in research settings, medical counseling services should be available to enable people to fully understand the results of their own genetic profile.
MsgId: *breakthrough(38)
Date: Wed Jun 4 22:08:36 EDT 1997
From: moderator At: 206.80.165.26
Are people in your field trying to influence legislation that adequately help workers on genetic testing issues?
MsgId: *breakthrough(39)
Date: Wed Jun 4 22:10:02 EDT 1997
From: Dr_McCunney At: 206.80.165.26
Yes, in general physicians are seriously concerned about misuse of genetic tests. In fact, many professional societies, including the American College of Occupational and Environmental Medicine have published position papers essentially calling for caution in the widespread application of genetic tests.
MsgId: *breakthrough(40)
Date: Wed Jun 4 22:13:20 EDT 1997
From: moderator At: 206.80.165.26
Do people ask you to check if they can genetically work with a material before they take a job?
MsgId: *breakthrough(41)
Date: Wed Jun 4 22:13:46 EDT 1997
From: guest At: 153.35.119.228
Under which conditions would physicians generally support genetic testing?
MsgId: *breakthrough(42)
Date: Wed Jun 4 22:15:08 EDT 1997
From: Dr_McCunney At: 206.80.165.26
At this point, no, in the context of my practice in occupational and environmental medicine, I haven't been asked to conduct a genetic profile. But there are certain physicians who specialize in genetics who will conduct genetic testing for risk of diseases such as Huntington's chorea, or certain familial types of colon cancer.
MsgId: *breakthrough(43)
Date: Wed Jun 4 22:16:13 EDT 1997
From: moderator At: 206.80.165.26
So people are still taking jobs that require working with hazardous substances and not asking any questions from their own end about whether they are at risk?
MsgId: *breakthrough(44)
Date: Wed Jun 4 22:17:50 EDT 1997
From: Dr_McCunney At: 206.80.165.26
They really don't ask for genetic tests. They may other types of questions, but they don't ask for that. They do ask whether materials or work duties pose special risks, whether they should take certain precautions. Occasionally they'll ask for test to determine whether they've had any health damage, even though they may not be aware of it. But at this point not specifically asking for genetic tests.
MsgId: *breakthrough(45)
Date: Wed Jun 4 22:18:50 EDT 1997
From: moderator At: 206.80.165.26
People are still taking jobs working with beryllium?
MsgId: *breakthrough(46)
Date: Wed Jun 4 22:20:21 EDT 1997
From: Dr_McCunney At: 206.80.165.26
An unanswered question, however, is whether work with beryllium, or any other hazard, even in the context of a genetic predisposition, is whether cancer will occur when exposure to the hazard is minimized.
MsgId: *breakthrough(47)
Date: Wed Jun 4 22:21:52 EDT 1997
From: moderator At: 206.80.165.26
Do you get contacted with industry to assess a situation? And do you get contacted by industry to help protect workers from risks?
MsgId: *breakthrough(48)
Date: Wed Jun 4 22:23:52 EDT 1997
From: Dr_McCunney At: 206.80.165.26
Yes, in addition to being referred individual patients, either on their own or through referral from other physicians, I also am contacted by industries who seem seriously concerned about preventing serious illness in their employees. For example, I may be asked about what type of medical program should be established to A. Insure that illness is prevented and B. That if there is an effect from exposure to a hazard, that it is detected early enough so that the person can be cured from the disease.
MsgId: *breakthrough(49)
Date: Wed Jun 4 22:24:40 EDT 1997
From: moderator At: 206.80.165.26
In general, is there a trend towards increased exposure to hazards, or increased healthy situations in industry?
MsgId: *breakthrough(50)
Date: Wed Jun 4 22:26:37 EDT 1997
From: Dr_McCunney At: 206.80.165.26
Yes, there are a number of trends worthy of comment. One, the major occupational illnesses in this century, such as those due to coal, silica, and asbestos have been reasonably well controlled and in some cases, virtually eliminated. The second major trend is across many industries, a reduction in exposure to potential hazards, through a combination of engineering controls and use of personal protective equipment.The third major trend is a much greater awareness on the part of employers of the potential health implications of certain industrial processes, and the use of certain materials. And the fourth trend is with the introduction of new materials that occurs on a continual basis. And despite the most sincere and intense premarketing testing, substances can simply not be tested in the laboratory for every conceivable health outcome. As a result, employers and employees now show greater vigilance than in the past towards the potential health implications of certain work assignments, whether in the use of new or old materials.
MsgId: *breakthrough(52)
Date: Wed Jun 4 22:33:48 EDT 1997
From: moderator At: 206.80.165.26
Thank you so much, Dr. McCunney , for joining me tonight. I know our viewers were concerned about the risks you discussed.
MsgId: *breakthrough(53)
Date: Wed Jun 4 22:34:30 EDT 1997
From: Dr_McCunney At: 206.80.165.26
Thank you, Madeleine, for the opportunity to participate in such an interesting program. It's been a pleasure.
MsgId: *breakthrough(54)
Date: Wed Jun 4 22:34:54 EDT 1997
From: moderator At: 206.80.165.26
Here also. Goodnight!
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