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18 MR. GOTTFRIED: Have you been sworn?

19 DR. BARKLEY: Yes.

20 MR. GOTTFRIED: Okay. Fire away.

21 DR. BARKLEY: Thank you. Thank you, Mr. Chairman and Members of the Assembly Health Committee for your willingness to learn as much as possible about Lyme disease, and particularly in your attempts to ascertain what you


1 can about the state-of-the-art information about Lyme
2 disease, which doesn't always include what is
3 published to date.
4 I am going to address some of the
5 unknowns in the area of Lyme disease and in
6 particular that having to do with the immunological
7 response of the individual to this infection, about
8 which we know very little. I'll be showing some
9 slides and I will make a copy of those available to
10 you at a later time. We also have a videotape which,
11 hopefully, will help explain some of the puzzling
12 information you've been hearing about why some
13 patients are seropositive for Lyme disease and other
14 patients remain seronegative for Lyme disease,
15 despite the fact that they clinically have been
16 defined and have been treated for -- defined as
17 having Lyme disease and have been treated for this
18 illness. If we could have the first slide? If you
19 could go back, please?
20 My interest in Lyme disease has to do
21 with some information that turned out to be rather
22 surprising - that I'm going to show you - indicating
23 that in some individuals and in women who have
24 regularly recurring menstrual cycles there seems to
25 be a dynamic between the hormonal status or the


1 endocrine status of the individual and the immune
2 system. For those of you who have never seen an
3 electron micrograph of Borrellia burgdorferi, this is
4 the spirochete known to be the infectious organism.
5 Here are spirochetes shown under dark
6 field microscopy in tissues.
7 This is a slide that shows the response
8 of the immune system in mice that are infected with
9 spirochetes. Basically, these mice were inoculated
10 with cultured spirochetes. And the spirochete load,
11 which increases here on this axis, is zero to a high
12 load. What is shown here is the response on the part
13 of the immune system. Secretions of something called
14 interleukin-1 are produced in response to infections.
15 This is a non-specific response and is one of the
16 immune system's cytokine responses to an infection,
17 whether it be viral or bacterial. What it signals is
18 activation of the host's immune response and can
19 induce fever. And as such, something like this
20 interleukin-1 is referred to as a pyrogen.
21 As you increase spirochete load in the
22 host, you see that there's an increase in the
23 response on the part of immune system and more
24 pyrogens, if you will, are produced, which are going
25 to induce fever. Fever is a sign of active


1 infection. If you challenge the immune system with
2 something called concanavalin A, which simply
3 stimulates further the immune system, you see that
4 you have a parallel but heightened response to the
5 presence of an increasing load of spirochetes in the
6 host. I apologize for the small size here of the
7 slides.
8 This shows the frequency of night
9 sweats, medically referred to as diaphoresis.
10 Diaphoresis simply refers to sweating. But one of
11 the hallmarks of infectious diseases has to do with
12 the occurrence night sweats and in some diseases the
13 recurrence of night sweats. Something like
14 tuberculosis was known centuries ago to have a bad
15 outcome in an individual if the clinician heard from
16 the patient that they were having -- he or she was
17 having night sweats every night. This meant that
18 most likely that individual would not survive the
19 illness. Malaria is known to induce these night
20 sweats; yellow fever. They're highly specific. They
21 don't occur in the daytime, they occur at night,
22 probably because that is when we have our lowest body
23 temperature and that is the period during which time
24 infectious agents multiple best. In individuals with
25 Lyme disease that we studied in a clinical study, we


1 found that 80 percent of these individuals did report
2 night sweat activity.
3 In this case study that I'm going to
4 show you, I would like for you to focus on a number
5 of things, but primarily the duration of symptoms and
6 the duration of treatment. Also, the pattern of
7 night sweat activity, in terms of intensity and
8 frequency, which is going to vary with time, but to
9 have a regular pattern to it, which you'll see
10 subsequently. Let's start with diaphoresis prior to
11 antibiotic therapy. So, this is an individual
12 diagnosed with Lyme disease, was having regularly
13 recurring menstrual cycles and was recording, in a
14 blind fashion, night sweat activity. This was
15 started, this recording of the data, to monitor the
16 individual's response to antibiotic therapy.
17 The individual wore the same night
18 garment and recorded the data in such a way that she
19 was not able to see the prior day's data. The
20 individuals who analyzed the data had no knowledge of
21 the study, so the analysis is a double-blind
22 analysis.
23 Notice that intensity of sweats,
24 changes -- and this is measured by the dampness of
25 the night garment, which we don't really have time to


1 discuss thoroughly, but I'll be happy to answer any
2 questions about this -- but the intensity of this
3 night sweat activity declines during this menstrual
4 cycle. What's shown in red is the day of menses,
5 which is considered the first day of menstrual cycle.
6 So, as you can see, prior to antibiotic therapy,
7 during this first period of observation, 40 days,
8 there is already a pattern to this night sweat
9 activity in this individual. It's highest shortly
10 after menses. It declines around the time of
11 ovulation, but after menses intensifies again.
12 Following the initiation of antibiotic
13 therapy something very surprising occurs, and that is
14 that you have both an intensification and a change in
15 this frequency of night sweat activity. Notice that
16 if you begin antibiotic therapy here, on day 42 of
17 this observation period, that between days 42 and 70,
18 in other words, for a solid month, this individual,
19 in terms of just this one criteria, night sweat
20 activity, which is a hallmark of an infectious
21 disease that is still active, is actually
22 intensified. It is not diminished in any way. The
23 natural pattern of the night sweat activity within a
24 menstrual cycle remains. And, indeed, this
25 individual does show some response to this


1 intravenous antibiotic therapy in that during the
2 following menstrual cycle the intensity of the night
3 sweat activity has decreased.
4 Now if we look at this same individual
5 for a period of 716 consecutive days, during which
6 time antibiotic therapy was provided not constantly -
7 this was an individual who, with her physician, was
8 attempting many times to refrain from antibiotic
9 therapy, but she went back on therapy because her
10 symptoms were not cleared - notice what you see.
11 Here is this period where you initiate antibiotic
12 therapy. You see that it takes over two years for
13 this individual to get to a baseline of prior health.
14 This individual never before she contracted Lyme
15 disease had any night sweats other than one night,
16 only in association with something like a viral
17 illness. Notice, however, that there is a linear
18 response to antibiotic therapy. This patient is
19 getting better.
20 If you look at the monthly pattern of
21 night sweat activity in association with menses, over
22 25 consecutive menstrual cycles in this individual,
23 with a mean menstrual cycle length of 28.5 days, what
24 you see is the intensification of night sweat
25 activity is indeed occurring around the time of


1 menses. If you look at the mean intensity of this
2 monthly pattern of night sweats, or diaphoresis, and
3 you study this in association with menstrual cycle
4 dynamics, what you see is that during the luteal
5 phase of the cycle - this defines the period after
6 ovulation, during which time the progesterone
7 secretion is highest - and you look at the mean
8 activity of night sweat activity during the
9 follicular phase, prior to the time of ovulation, you
10 see that there really is not much difference in the
11 intensity of the night sweats or immune system
12 activity. Rather, there is a period known as the
13 immune response interval that is occurring
14 approximately three days prior to, including the day
15 of menses, and three days thereafter.
16 If you then take the data and look at
17 the pattern of estradiol secretion in normal women
18 versus the pattern of night sweat activity in women
19 with Lyme disease, what you see is, indeed, at the
20 time that you see a decline in ovarian hormone
21 production, in terms of estradiol secretion and
22 progesterone secretion, which is the hallmark of the
23 period prior to menses, this is when you see
24 intensification of the immune system response.
25 Let's return now to the overall data.


1 This is de-trended to remove the effect of antibiotic
2 therapy in the initial stage of the study. What you
3 see, as I mentioned before, is a linear decline in
4 night sweat activity, and you see a periodicity of
5 night sweat activity in association with cycles
6 having to do with ovarian function. If you construct
7 a mathematical model based on this period of immune
8 response to Borrellia burgdorferi infection and you
9 model this infection with an attempt to estimate
10 spirochetal load - recall the very first slide that
11 showed you that the increase in cytokine response
12 occurs with increased with spirochetal load - what
13 you see is a surprising fit of the model, in terms of
14 spirochete load as influencing immune response to
15 that load, with the actual data that were obtained in
16 this case study.
17 It's very clear that we know very
18 little about individual immune system responses to
19 infectious diseases. It's a terrible thing to have
20 to say that we have AIDS to thank for our interest
21 and our study of the immune system. We know very
22 little about it. We know that it will, without its
23 normal function, lead to our death in this terrible
24 disease called AIDS.
25 We're going to see now a videotape


1 provided by Dr. David Dorward, whose research was
2 funded by the National Institutes of Health. And
3 basically this videotape shows what happens when a
4 spirochete comes into contact with a human T-cell
5 lymphocyte, an immune system cell.
6 (The videotape was played.)
7 "We're honored and happy to have him
8 here today. He's going to talk about lymphocytic
9 tropism by Borrellia burgdorferi.
10 Dr. David Dorward is a microbiologist
11 and facility manager of the Electron Microscopy
12 Facility for the National Institutes. For a period
13 of time, it appears that the cells can be lyased and
14 the spirochetes unscathed. The other type of
15 interaction seems to be very different, in which the
16 spirochete can penetrate. And it emerges rather
17 rapidly. I'll show you some more photographs of
18 this. This is the mechanism that I said I'd get back
19 to, in which we saw a spirochete that appeared to be
20 attached at one point and then invert itself. We
21 think what's going on here is that the spirochete is
22 actually penetrating and bringing with it some of the
23 cell membrane. And as it escapes, it escapes and
24 encloses itself within an envelope, if you will, of
25 the host cell membrane.


1 "The first part of this, we'll see that
2 this spirochete seems to swim around and bang into
3 the membrane of the cell, if you will. And then the
4 cell will lysis at about this position and the
5 membrane will peel back.
6 "Okay. So, in that interaction it was
7 cytotoxic for the cell.. And the cell rised and that
8 cell -- it may have been functionally dead before the
9 lysis occurred. But clearly that cell did not
10 survive the interaction.
11 "And it doesn't seem as if the
12 lymphocyte has much to do with this interaction.
13 It's rather -- we believe it's driven by the motility
14 of the spirochete. And the spirochete, as you can --
15 this is a static example of what we think we saw in
16 the video, in that the spirochete seems to penetrate
17 and simultaneously, or very shortly thereafter,
18 emerge. And if you can kind of envision the fact
19 that this is clearly penetrating into a pit -- and
20 then as it emerges, it seems to pull with it material
21 from the surface of the lymphocyte, and then the
22 outer membrane of the spirochete completely encircled
23 what appears to be two layers of lymphocytic membrane
24 with a layer cytosome in between.
25 "And I have shown this many panels just  


1 to get across the idea.
2 "So, I want to switch gears to the
3 in-vivo work. Recently, we have tried to develop a
4 system, or we worked to develop a system, for
5 studying to determine whether this interaction occurs
6 in vivo and what its effects may be. And what we saw
7 was that, indeed, the spirochetes bind to the
8 lymphocytes. They're immobilized on this approach.
9 And we think this is pretty strong evidence that --
10 at least in a mouse model, there is a good likelihood
11 or -- a good likelihood that direct interactions of
12 the spirochete and the lymphocytes do occur if they
13 attach to the lymphocytes; second, they might be
14 inside the lymphocytes; and third, they might have
15 acquired this layer of lymphocytic membrane around
16 them, which would enable them to stick.
17 "So, in conclusion, we coined the term
18 'lymphotropic' to describe the fact that spirochetes
19 do apparently find lymphocytes in vivo -- or in vitro
20 and in vivo. Second, spirochetes that are
21 lymphotropic are infectious, and this property --
22 spirochetes that are lymphotropic also disseminate
23 rapidly during a mammalian infection and they are
24 able to produce a persistent infection. I guess I
25 didn't stress that, but some of the mice were


1 positive out of the three-week period, which in a
2 mouse is considered a persistent or systemic
3 infection.
4 "It appears also that the factors that
5 mediate this interaction between spirochetes and
6 lymphocytes may be inducible in vivo. They are
7 clearly selectable in vitro, but we do not know yet
8 what may be occurring in a mammalian infection to
9 stimulate the spirochetes to interact with the
10 lymphocytes, although that is not clearly a matter of
11 considerable interest, and that the lymphocytes and
12 lymphatic tissues may constitute new niches - rather
13 an ironic niche, if you will - as the cells that are
14 supposed to help us protect ourselves from infection
15 may actually be a preferred niche for the spirochete
16 in mammalian infections."
17 (The videotape was stopped.)
18 DR. BARKLEY: Dr. Dorward was,
19 unfortunately, not able to be here today, but his
20 work has really helped us get a better understanding
21 of the variability in the response of the individual
22 to infections in general and, in particular, in
23 response to Borrellia burgdorferi infection.
24 What I want to emphasize are some key
25 points. One is that currently the state-of-the-art


1 information indicates that we don't know what all of
2 the risk factors are for the development of Lyme
3 disease. We know that individuals differ in their
4 genetic makeup. And I can tell you from years of
5 studies with inbred strains of mice that even in
6 mammals, that share 95 percent of identical genes,
7 which you'll never find in the wild population --
8 even in mammals like mice that have been genetically
9 selected for laboratory studies, that differ only in
10 a matter of few genes, you see individual variation
11 in endocrine responses and most likely in
12 immunological responses as well.
13 So, we simply don't have all of the
14 information to allow us to even define why it is that
15 some individuals are bitten by ticks, exposed to
16 Borrellia burgdorferi infection, and don't develop
17 any symptoms; other individuals can get a tick bite,
18 be seronegative, and have profound illness, profound
19 symptoms associated with Lyme disease. Why it is
20 that certain individuals do seem to respond
21 reasonably well to a short course of oral antibiotics
22 and others seem to fail this very same treatment --
23 we don't know why it is that certain individuals
24 develop persistent symptoms that probably mean
25 persistent infection. There's a lot of controversy


1 about whether or not persistent symptoms reflects
2 some change in the immune system of the individual
3 who has had exposure to the bacterium.
4 We don't know if, in certain
5 individuals, once you get the spirochetes into your
6 systemic circulation, your immune system clears this
7 infection for you in a very short period of time, or
8 whether or not, as Dr. Dorward's work would suggest,
9 in certain individuals the spirochetes have become
10 the stealth bacteria in the sense that they can
11 burrow through a T-lymphocyte, coat themselves with
12 human proteins and evade an immune system response,
13 allowing them then to penetrate issue areas of the
14 body which are not subject antibiotic penetration,
15 nor to killing by the immune system.
16 We know that there are many
17 immune-privileged sites within the human body, and we
18 know that antibiotics don't penetrate these sites
19 unless, for example, they are inflamed, which isn't
20 always the case. We also know that syphilis, which
21 is also caused by spirochetal organism, differs very
22 much in terms of this organism's response in culture
23 versus in vivo. Treponema pallidum, which is the
24 infectious agent causing syphilis, will not even
25 survive in culture, whereas Borrellia burgdorferi


1 will survive up to ten months without even undergoing
2 a division. What do you imagine it might do actually
3 in the host in ideal situations? So, we don't even
4 know thing about the life cycle characteristics of
5 Borrellia burgdorferi in the human host.
6 You've already heard a lot about their
7 having -- one our major problems is the lack of a
8 standard laboratory diagnostic test. There is no
9 gold standard to show that you have Lyme disease, nor
10 to monitor your response to antibiotic therapy. The
11 response to antibiotic therapy is provided by the
12 patient, who is reporting his or her symptoms and how
13 he or she is responding to treatment. We don't
14 anything, really, about the dynamics of bacterial
15 survival or reproduction in the human host.
16 So, there is a large degree of
17 uncertainty in biological systems. And we're seeing
18 this beautifully illustrated in Lyme- and
19 tick-related diseases. We also know that science is
20 not exact and that medicine is considered an artful
21 science. And the diagnostics and the treatments
22 currently used in Lyme disease certainly do reflect
23 this interaction of art and science, which is not
24 exact. This is why I think you're hearing so much
25 diversity of opinion on the part of the medical


1 community as to what constitutes safe and responsible
2 treatment. Some clinicians know that their patients
3 remain ill if they are not provided antibiotics for
4 their Lyme disease symptoms -- so ill that they
5 cannot maintain employment. The majority of opinion
6 is based on, as you've heard, evidence-based medicine
7 and guidelines established by evidence-based
8 medicine. Unfortunately, because of the ethical
9 considerations involved in performing human studies,
10 we really do not have information about Lyme disease,
11 how best to treat this, and what the actual responses
12 are to antibiotic therapy. We hope Dr. Fallon said
13 he would provide us with additional information.
14 It's very interesting that two recent
15 publications in the New_England_Journal_of_Medicine,
___ _______ _______ __ ________
16 the July 12th issue, are providing us, indirectly,
17 some of the most important information that we have
18 yet about Lyme disease.
19 The first of these studies was
20 performed in Westchester County, New York and had to
21 do with providing a single dose of doxycycline to
22 individuals that had removed a tick within 72 hours
23 from the tick bite. What's interesting about this
24 study is that the individuals included in the study
25 had a baseline average seropositivity rate of 17


1 percent. Yet, in this study, performed for a
2 six-week period of time, all subjects showed at best
3 a three percent rate of seropositivity. So, what
4 intrigued me about the study in the publication was
5 mentioning that they expected infection rates in the
6 neighborhood of five percent in Westchester County.
7 This study took place over several years and had 482
8 individuals included, I believe -- something around
9 that number. So, if you looked at just the numbers,
10 they should have expected 170 out of a 1,000
11 individuals to have Lyme disease if they were
12 sampling an unbiased population from Westchester
13 County described as a highly endemic area for Lyme
14 disease. And, yet, in this study only 30 individuals
15 had Lyme disease, developed Lyme disease by the
16 criterion of this seropositivity. So, they were off
17 140 individuals. And this was a study with large
18 numbers included.
19 The second article that appeared,
20 actually following, back to back, the first article
21 that I referred to, is the publication that has been
22 referred to today already, performed by Dr. Klempner
23 and others. And Dr. Phillips very astutely pointed
24 out one of the major problems with that study. It
25 has to do with selection of patients for inclusion in


1 the study. You've seen today that in certain
2 individuals, even in the face of constant -- nearly
3 constant, I should say, antibiotic therapy - and that
4 two-year period involved intravenous IV therapy -
5 symptoms persisted, as did illness. This individual
6 remained ill for over a year. But this individual in
7 long-term follow-up has no night sweat activity now
8 because of, in her opinion, long-term antibiotic
9 therapy. So, what is wrong with the Klempner study?
10 First of all, the criterion for
11 inclusion had to do with prior antibiotic therapy.
12 You had to have Lyme disease and you had to have
13 already been treated with the standard
14 medically-approved, by guidelines, antibiotic course.
15 These were individuals who had failed that therapy
16 already. That's what you had to have as an inclusion
17 criterion to be in the study. Therefore,
18 unfortunately, we really cannot draw any conclusions
19 from this study, because it isn't the study that we
20 need to be performing. It's a study that, as others
21 have pointed out already, was designed improperly.
22 And I don't think that was intentional. I think it
23 was simply people not seeing the forest for the
24 trees, so to speak.
25 I have some additional points I'd like


1 to make about this study.
2 One of the important points is that to
3 monitor infection only fluid samples were obtained;
4 either blood sample for serology or spinal fluids,
5 cerebral spinal fluid, for either PCR analysis or
6 antibiotic -- excuse me, not antibiotic, but antibody
7 response. Yet, it's very well established that
8 Borrellia burgdorferi can survive in tissues. And,
9 unfortunately, that is another major problem with the
10 study. But this is a problem that we have in
11 general. It's going to be very difficult to actually
12 perform that type of invasive study on human
13 volunteers, and it's going to be difficult to get a
14 Human Subjects Approval Committee to allow you to
15 perform a long-term placebo versus antibiotic treated
16 study for Lyme disease because of the now recognized
17 devastation this disease can lead to for an
18 individual.
19 The other problem -- or there are
20 several problems, but another has to do with the lack
21 of mention of co-infections. We don't have time to
22 really deal with these. Unfortunately, I will not be
23 saying anything more than that, simply that that
24 wasn't addressed, and that's in the only
25 placebo-controlled study we have so far. It was not


1 a long-term study. It's described as a long-term
2 study, but in fact it is not. Thirty days of IV
3 therapy followed by eight weeks of oral antibiotic
4 therapy is not a long-term study -- not based on what
5 you've seen today in terms of how certain individuals
6 respond to long-term antibiotics. They have
7 persistent symptoms even while on antibiotics.
8 Another problem is that there is
9 something called Jarisch-Herxheimer reaction that can
10 occur when you have a bacterial infection and it is
11 initially treated with antibiotics. Because you are
12 killing the bacteria in the presence of antibiotics,
13 this can heighten the immune system response.
14 Whether or not the Jarisch-Herxheimer reaction
15 remains as potent with subsequent exposure to
16 antibiotics for the same organism is uncertain. In
17 other words, it's possible, since the patients in the
18 Klempner study had already been exposed to
19 antibiotics, that they would not necessarily have
20 been able to monitor in a subjective fashion whether
21 or not they were improving with antibiotics or they
22 were getting worse.
23 The neurological scales that were used
24 in this study were insufficient to assess impairment
25 and psychiatric dysfunction. This was a subjective


1 assessment scale that was used, rather than adequate
2 objective measures, which were not employed to the
3 extent that would really allow these investigators to
4 assess clinical status.
5 A final but minor point has to do with
6 the fact that the placebo versus the antibiotic
7 treated patient seemed to have different scores on
8 the primary outcome measures, suggesting that the
9 randomization of subjects may have been inadequate.
10 And, finally, long-term follow up with
11 these patients was not provided.
12 I hope that this has provided you with
13 useful information. Thank you.
14 MR. GOTTFRIED: Okay. Thank you. That
15 was very helpful, especially the critique of the
16 Klempner study.
17 Questions?
18 MS. O'CONNELL: Yes. Thank you,
19 Richard.
20 Can I summarize it this way and then
21 maybe you can correct inaccuracies? The presentation
22 you made with regard to the immune system and the
23 different levels of response in patients who may be
24 dealing with, you know, an infection like Lyme
25 disease -- from what you're saying, it seems to me


1 that it would appropriate, then, to allow the
2 physician's judgment to really play the key role in
3 terms of the duration of antibiotic treatment, given
4 that the immune system's response can be so variable
5 from individual to individual, based on many factors,
6 as you were pointing out; that there is no -- and
7 from what we've heard earlier this morning, there is
8 no gold standard of care or of really diagnosing this
9 disease with any kind of degree of certainty.
10 So, would you agree that physician's
11 judgment at this juncture in time, with regard to the
12 duration of the antibiotic therapy, based on the
13 clinical symptoms that the patient is experiencing,
14 is really the best form of treatment at this point,
15 given the availability of whatever studies we have or
16 lack of studies that we have at this juncture?
17 DR. BARKLEY: I agree absolutely that
18 this should definitely be a disease that is
19 considered undefined, the treatment for each
20 individual that is going to be efficacious is
21 unknown, and that this should be a patient-physician
22 interaction and decision. It should not in any way
23 be influenced by outside parties unless the patient
24 complains or there are objective reasons for review,
25 an external review.


1 MS. O'CONNELL: Thank you. Thank you
2 very much.
3 DR. MILLER: Just one other comment.
4 And I want to thank you for having presented that as
5 clearly as you did.
6 Earlier on when we heard from some of
7 our experts that the six weeks constituted long-term
8 therapy, it was nice to see that you were able to
9 correlate a symptom of infection over time. And in
10 your study it took two full years before those
11 symptoms of infection were dissipated. So, it gives
12 us a much better understanding of what "long term"
13 really means and how flawed the arguments are when
14 they talk about long term being six weeks. And I
15 think that's an important aspect. Sometimes it just
16 takes longer than some people would expect to get the
17 results they wanted, and so we have to give a lot
18 more latitude to the health care providers. So, I
19 thank you for that. That was a well-done study.
20 DR. BARKLEY: Well, I thank you for
21 your comments. Because I really want to emphasize
22 that the Westchester County study is very critical.
23 We need to really look at this carefully. These were
24 individuals going into their physician with a tick
25 that they have removed. And if you look at the rate


1 of infectivity of these individuals, what it tells
2 you at face value is that most of these individuals
3 aren't getting Lyme disease. But I don't think that
4 we can say that at all. I, unfortunately, don't know
5 what the rate of tick infection is in Westchester
6 County, and that's a flaw in that particular study.
7 This was not addressed. These individuals did not do
8 anything other than measure the size of the tick, if
9 you will, to get an idea of engorgement of the tick
10 with blood to see how long then that reflected
11 presence on the host. But, yet, with this careful
12 study there was not an attempt to determine if those
13 ticks had Borrellia burgdorferi infections.
14 So, at first glance, one would say
15 since we know that in certain areas on Long Island 80
16 percent of the ticks are carrying Lyme disease, I
17 would venture to guess that the rate of infectivity
18 of the ticks in Westchester County is a lot more than
19 five percent. A lot higher, I would think. Does
20 anyone happen to know what those data are?
21 At any rate, the point is this: These
22 were individuals that did have tick bites, and yet
23 most of them did not develop symptoms of Lyme
24 disease. The most important finding in this study is
25 that this rash associated with Lyme disease did not


1 appear frequently at all. Most likely, because data
2 like this exists from the State of Wisconsin, it's
3 true that most individuals who get bitten by a tick
4 that carries Borrellia burgdorferi do not develop
5 signs of the infection because their immune system
6 responds to that insult and clears the infection. It
7 may very well be the case that any individual who
8 develops the symptoms of Lyme disease is the
9 exception to the rule. No wonder, then, we have such
10 a range of variation in response to the infection.
11 If it is the case that hundreds of individuals in
12 Westchester County were bitten by these ticks that
13 most likely were carrying Lyme disease, the
14 overwhelming majority of them developed no symptoms.
15 And so I would like to leave you with
16 the suggestion that there is a spectrum of response
17 if you develop any symptoms at all that are related
18 to Lyme disease and Borrellia burgdorferi infection;
19 that that represents a continuum of something like
20 individual genetic immune system interaction with the
21 infection. And that at one end of that spectrum
22 you're going to have individuals who are going to
23 have a very serious illness that can be fatal, and to
24 deny those individuals therapy because of
25 well-established medical guidelines would be


1 absolutely a tragedy.
2 MS. O'CONNELL: Doctor, I just want to
3 follow up on what you just said. One of the things
4 we've seen and heard about in our capacity in the
5 State Legislature, from some of the physicians who
6 have been -- whose conduct and care and treatment has
7 been reviewed by the state agencies, was that a
8 patient came in and it was documented that the
9 patient had complained of an episode of dizziness.
10 Well, that physician didn't order a neurological
11 workup, which, you know, it was determined may have
12 violated or breached the standard of care, so to
13 speak.
14 But what I'm gleaning from what you're
15 saying is that you can have a panoply of symptoms
16 here, ranging from extremely mild or subclinical, so
17 to speak, to very acute, and that panoply of symptoms
18 can range to include the neurological system, you
19 know, and various other organ body symptoms, so that
20 we cannot pigeonhole the treatment and the workups
21 with -- involving, you know, the management of a Lyme
22 disease case into any one area. That it's really a
23 course of conduct or a course of presentation or a
24 course of symptomatology over a period of time that a
25 physician or provider who is caring for that patient


1 needs to evaluate, in terms of their overall disease
2 during the course of the time that they are receiving
3 treatment for that disease, and gauge the treatment
4 according to those symptoms, with regard to that
5 individual patient and the patient's needs. Would
6 you agree with that or would you make a comment on
7 that?
8 DR. BARKLEY: I agree wholeheartedly.
9 And this is exactly - and you have put it very
10 succinctly - why grassroot, to use that term,
11 physicians who treat, who are in the trenches
12 treating the patients with Lyme disease, tell you
13 it's a clinical diagnosis. And what you look for is
14 the patient's response to therapy. We now have far
15 too many individuals, that are highly credible
16 individuals with longstanding Lyme disease, who have
17 lost employment, all the way from university
18 professors, M.D.s, professionals, computer experts --
19 and your level of education should have absolutely
20 nothing to do with something like your employment --
21 well, let's see. Wait a minute, let me retract that.
22 What I'm trying to say is that each and
23 every patient deserves the same treatment regardless
24 of how -- what their background is when they come to
25 the physician. And, actually, Lyme disease, I hope,


1 is going to provide us the model for understanding
2 human disease. We have -- we're on the forefront of
3 discovery. We are seeing that there is no easy
4 answer. You're right, we cannot pigeonhole symptoms
5 necessarily.
6 And what we've heard all day long is
7 about evidence-based medicine and about being a
8 responsible physician, and this is based on tradition
9 and what physicians were trained to practice. And
10 Dr. Phillips pointed out that it takes a long time to
11 get people to change their approach. We're in the
12 dinosaur age of medicine. The time will come when
13 you will scrape a little cell from inside someone's
14 cheek, or get cord blood from the newborn, and you'll
15 be able to predict that individual's disease
16 susceptibility, and how to prevent the diseases from
17 developing, and what will be an individualized
18 treatment for that individual. And that is what Lyme
19 disease is telling us. There is no gold standard for
20 treatment, just as there is no gold standard for
21 diagnosis.

22 MS. O'CONNELL: Thank you, Dr. Barkley,

23 for your presentation. Thank you very much.