15 MARILYNN BARKLEY, M.D.; Sworn

16 DR. MARILYNN BARKLEY, RESEARCHER,

17 UNIVERSITY OF CALIFORNIA AT DAVIS: Thank you.

18 MR. GOTTFRIED: Have you been sworn?

19 DR. BARKLEY: Yes.

20 MR. GOTTFRIED: Okay. Fire away.

21 DR. BARKLEY: Thank you.

22 Thank you, Mr. Chairman and Members of

23 the Assembly Health Committee for your willingness to

24 learn as much as possible about Lyme disease, and

25 particularly in your attempts to ascertain what you

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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

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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

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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

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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

204

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

205

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

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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.

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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

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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.

209

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

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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

211

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

212

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

213

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

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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

215

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

216

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

217

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

218

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

219

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

220

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

221

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.

222

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

223

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

224

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

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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

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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,

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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.