0:00:06.859,0:00:10.379
Good evening.

0:00:10.380,0:00:13.410
thank you no doubt for

0:00:13.410,0:00:17.119
Thank you Nora, for making possible this's evening's

0:00:17.119,0:00:20.560
hopefully dialogue. Chronic fatigue syndrome

0:00:20.560,0:00:23.660
is arguably one of the most

0:00:23.660,0:00:27.519
controverted, misunderstood, misperceived

0:00:27.519,0:00:32.119
fields in medicine today. Although

0:00:32.119,0:00:36.550
it is clear that the health of millions of people

0:00:36.550,0:00:40.700
has been compromised significantly by this disease,

0:00:40.700,0:00:44.510
still, in medicine, we face situations

0:00:44.510,0:00:49.190
where an extreme, even in our own medical community--

0:00:49.190,0:00:52.190
the diseased is not believed, that it is real.

0:00:52.190,0:00:56.180
Which is a shame. So the one thing, if there is one thing

0:00:56.180,0:01:00.260
of anyone in this audience here today, that I would like to

0:01:00.260,0:01:05.890
have us a point to take home, of your family members, your friends, or yourself,

0:01:05.890,0:01:09.880
is to not kid yourself--this is a real disease.

0:01:09.880,0:01:13.920
And what I would like to do tonight is share with you

0:01:13.920,0:01:17.400
the evolving understanding

0:01:17.400,0:01:22.119
that here at Stanford we have put together. What we tell you today

0:01:22.119,0:01:26.100
may not be true tomorrow, but what we tell you today

0:01:26.100,0:01:30.530
hopefully is better than what we had as a model or as an understanding

0:01:30.530,0:01:34.200
yesterday. And it is evolving. It's changing.

0:01:34.200,0:01:37.289
But we have a simple goal, is--one day,

0:01:37.290,0:01:41.360
one day, have CFS,

0:01:41.360,0:01:46.600
a history of the past, so we do one day be able

0:01:46.600,0:01:51.619
to conquer the disease, and be able to bring relief finally to the many patients

0:01:51.619,0:01:52.450
who are suffering.

0:01:52.450,0:01:56.390
I do not have the time frame for this, but trust me,

0:01:56.390,0:01:59.600
we are working hard in making that time frame

0:01:59.600,0:02:03.119
the shortest possible. Allow me to start the

0:02:03.119,0:02:06.549
presentation with a real case. This is a patient--

0:02:06.549,0:02:11.540
I don't know if she's in the audience or not--but it's a 53-year-old woman

0:02:11.540,0:02:14.709
who came to see us in 2008

0:02:14.709,0:02:18.150
because she had had disabling fatigue

0:22:44.990,0:22:48.400
of treatment. And what they found, if they gave

0:22:48.400,0:22:52.220
the drug or placebo--so they would randomize to drug

0:22:52.220,0:22:56.100
for month-and-a-half, or placebo for month-and-a-half,

0:22:56.100,0:22:59.209
what they found is that there was no difference. But just

0:22:59.210,0:23:03.100
put that in the in the back of your brain. The fact

0:23:03.100,0:23:06.230
that that patient, those patients, got a month-and-a-half

0:23:06.230,0:23:09.669
of antiviral treatment, or acyclovir.

0:23:09.669,0:23:13.340
So the one thing that we changed at Stanford about

0:23:13.340,0:23:17.100
seven years ago, was that we

0:23:17.100,0:23:20.450
brought a new model. And we

0:23:20.450,0:23:24.679
thought if the patients have been here for a long period of time,

0:23:24.679,0:23:29.000
and if it's possible that an infectious agent is behind the symptoms

0:23:29.000,0:23:32.120
at a chronic level, will it be possible that

0:23:32.120,0:23:36.350
if we intervene with the appropriate agent--and finding that appropriate agent

0:23:36.350,0:23:37.309
may be a really

0:23:37.309,0:23:41.710
daunting task--is it possible that then long-term,

0:23:41.710,0:23:46.409
with appropriate anti-microbial interventions, can improve the symptoms

0:23:46.409,0:23:50.330
in subsets of patients, not to repeat the mistakes of the past,

0:23:50.330,0:23:54.350
of treating all the patients as the same homogeneous group.

0:23:54.350,0:23:57.658
And to our surprise, when we took patients and--

0:23:57.659,0:24:00.890
it's beyond the scope of tonight's conversation on how we

0:24:00.890,0:24:06.260
ran into this surgroup--we found that if patients had high levels

0:24:06.260,0:24:10.720
of antibodies against Epstein-Barr virus, the same virus that has been

0:24:10.720,0:24:14.870
clearly tied to the onset of CFS, and another virus

0:24:14.870,0:24:18.600
called Human Herpesvirus-6, if they have high levels against

0:24:18.600,0:24:21.830
those two viruses, it looks like when we gave them

0:24:21.830,0:24:25.210
another drug called Valganciclovir

0:24:25.210,0:24:28.409
for six months in this abscissa. You have

0:24:28.409,0:24:33.320
a year's, so goes all the way to six months, half a year here,

0:24:33.320,0:24:37.830
and in the same abscissa, but for when the patients were starting before therapy,

0:24:37.830,0:24:41.600
you have all the way up to twenty years. So the patient may have been sick for

0:24:41.600,0:24:42.379
eighteen years,

0:24:42.380,0:24:46.460
one year, five years--no matter how long they were sick

0:24:46.460,0:24:49.580
when we gave this drug for six months,

0:24:49.580,0:24:54.490
total surprise to us. They had this remarkable

0:24:54.490,0:24:58.529
improvement in their physical and cognitive

0:24:58.529,0:25:03.900
function. And to our surprise as well,

0:25:03.900,0:25:06.279
the initial reaction to

0:25:06.279,0:25:13.210
them was, they got worse. And then they improved.

0:25:13.210,0:25:17.320
The worsening was a complete surprise to us. And we made a mistake initially

0:25:17.320,0:25:21.879
because we let people believe that for patients to get

0:25:21.880,0:25:25.529
better with this intervention who had these markers in the blood,

0:25:25.529,0:25:29.800
they had to get worse. And that later on

0:25:29.800,0:25:32.600
turns out to be not correct. There are patients who can get better

0:25:32.600,0:25:36.340
without significant worsening, but still we see patients who get worse

0:25:36.340,0:25:40.490
with the initial treatment. Now, we cannot

0:25:40.490,0:25:45.200
be certain that this would have not been done because we perhaps

0:25:45.200,0:25:46.529
validated the patients; we

0:25:46.529,0:25:50.580
listened to them, so that we were doing a placebo effect.

0:25:50.580,0:25:54.370
It's hard to argue that this is placebo when somebody has been sick for

0:25:54.370,0:25:55.449
twenty years,

0:25:55.450,0:25:59.900
or eighty years, they get an intervention for six months, and they suddenly get better.

0:25:59.900,0:26:03.290
But granted, we have to go to what is called a

0:26:03.290,0:26:06.450
randomized, placebo-controlled double-blind

0:26:06.450,0:26:10.460
pilot study, to see if we could give the drug

0:26:10.460,0:26:14.279
to patients when they didn't know they were getting the drug,

0:26:14.279,0:26:17.330
or the sugar pill, and we the physicians

0:26:17.330,0:26:20.490
will not know the same thing. So: double-blind.

0:26:20.490,0:26:25.000
And we were fortunate to have the sponsorship.

0:26:25.000,0:26:28.840
The answer for many of the questions we face

0:26:28.840,0:26:32.539
with chronic fatigue syndrome is doing clinical trials, but those are

0:26:32.539,0:26:35.890
very expensive things to do, enterprises to do,

0:26:35.890,0:26:39.779
and we were lucky that we had the sponsorship from the manufacturer

0:26:39.779,0:26:42.919
of the drug in this case. Like any

0:26:42.919,0:26:46.980
intervention, we do need a team.

0:26:46.980,0:26:50.750
Nothing can happen these days in research without having

0:26:50.750,0:26:54.210
an outstanding team. And what we did is

0:26:54.210,0:26:58.440
randomized the patients to two areas: to either placebo,

0:26:58.440,0:27:02.270
sugar pill, or valacyclovir for six months,

0:27:02.270,0:27:06.200
and then for three months we stayed blind still.

0:27:06.200,0:27:10.220
At nine months, we took the data, put it in

0:27:10.220,0:27:13.610
three CVs, shipped it to three different,

0:27:13.610,0:27:17.209
three different places, so that nobody could touch the data

0:27:17.210,0:27:20.210
after the blind code was broken,

0:27:20.210,0:27:23.529
and then we broke the code and see how the patients did

0:27:23.529,0:27:27.390
on the drug versus the sugar pill.

0:27:27.390,0:27:31.260
This is a graph that shows what happened

0:27:31.260,0:27:34.710
to the patients who are either on the

0:27:34.710,0:27:39.289
placebo in red, or who are on the treatment

0:27:39.289,0:27:42.460
in green. And in this scale,

0:27:42.460,0:27:46.230
going down means you are getting better.

0:27:46.230,0:27:49.270
So the patient who went on the treatment went down,

0:27:49.270,0:27:52.360
meaning they got better, and that

0:27:52.360,0:27:55.459
trend of going down was

0:27:55.460,0:27:59.110
according to this statistical model, it's statistically significantly

0:27:59.110,0:28:02.990
different than those in the placebo, suggesting here

0:28:02.990,0:28:07.190
that the benefit that we have shown before, when we were giving this drug to

0:28:07.190,0:28:08.149
patients,

0:28:08.149,0:28:12.120
is mediated by something that the drug is doing, and not something that they

0:28:12.120,0:28:12.870
are doing

0:28:12.870,0:28:18.800
themselves through placebo. We also assessed

0:28:18.800,0:28:22.189
their cognitive function, meaning we asked the patients

0:28:22.190,0:28:26.290
how they felt in terms of their cognitive performance.

0:28:26.290,0:28:29.720
And they say, I feel 100 percent, which no one will tell us

0:28:29.720,0:28:33.429
when they were sick, or they will say 10 percent or 50 percent and so forth.

0:28:33.429,0:28:37.820
That is very hard to correlate, because it also depends on how

0:28:37.820,0:28:41.408
good their sleep (is) or what other medications they are taking.

0:28:41.409,0:28:44.630
et cetera. So when we looked at

0:28:44.630,0:28:47.909
what happened with their cognitive function--self-reported,

0:28:47.909,0:28:51.110
but remember, under double-blind conditions, not knowing if they were

0:28:51.110,0:28:52.600
getting treatment or placebo--

0:28:52.600,0:28:56.779
the trajectory also for those who went into treatment

0:28:56.779,0:29:00.510
was better that those who were in the placebo.

0:29:00.510,0:29:03.669
Now is one of those things--

0:29:03.669,0:29:09.120
the research--never stops either surprising you or fascinating you.

0:29:09.120,0:29:13.610
The randomization for this study, meaning we allocated the patients

0:29:13.610,0:29:17.729
to either group by pure chance--

0:29:17.730,0:29:20.760
the allocation of the patients to the two groups

0:29:20.760,0:29:25.158
was done by somebody in Geneva, in Europe. So we will see a patient

0:29:25.159,0:29:28.419
and we'll say, "That patient is a candidate for the study."

0:29:28.419,0:29:32.710
We didn't allocate them to one group or the other. We will call Geneva, to a

0:29:32.710,0:29:33.679
group there,

0:29:33.679,0:29:36.929
and they would give us the answer the next day, or whatever time difference it was,

0:29:37.299,0:29:41.220
and they would tell us, "This is the group the patient should go, group X."

0:29:41.220,0:29:44.299
And they would call pharmacy and they would give us the appeals for that

0:29:44.299,0:29:48.360
patient and so forth. Yet, despite that it was

0:29:48.360,0:29:52.290
totally by chance and by pure randomization,

0:29:52.290,0:29:55.279
if you'll notice, here, the baseline

0:29:55.279,0:30:00.590
levels of cognitive function for the treatment group is slightly lower

0:30:00.590,0:30:04.370
than the placebo. We were fortunate that that this was not statistically

0:30:04.370,0:30:09.490
significant, but the patients in the treatment group started with a slight

0:30:09.490,0:30:10.800
disadvantage

0:30:10.800,0:30:14.340
over the placebo. And the same thing actually was for the fatigue.

0:30:14.340,0:30:19.800
Remember that in this scale, I mentioned to you that the higher the worse,

0:30:19.800,0:30:22.199
and again, the patients,

0:30:22.200,0:30:25.559
well in this case, you know, the lower is the better, so the treatment is

0:30:25.559,0:30:27.928
started at the right place.

0:30:27.929,0:30:32.279
And then the other aspect that we did was to see how the cognitive did by

0:30:32.279,0:30:35.659
a questioner. So the previous light was how they did

0:30:35.659,0:30:39.290
with self-reported cognitive function; this is how they do

0:30:39.290,0:30:42.500
with a questioner that assesses their mental capacity,

0:30:42.500,0:30:46.289
and in this case, going down again is improving

0:30:46.289,0:30:50.210
and again the treatment group is slightly worse

0:30:50.210,0:30:53.419
than the starting place for the placebo,

0:30:53.419,0:30:56.570
yet the trajectory of the treatment group

0:30:56.570,0:31:00.279
is statistically significantly better--going down it's better--

0:31:00.279,0:31:03.440
than the placebo group. So in this study we

0:31:03.440,0:31:06.630
offer perhaps what are the first

0:31:06.630,0:31:11.290
evidences that if you intervene with an appropriate drug,

0:31:11.290,0:31:14.110
with a specific biomarker in black like titers

0:31:14.110,0:31:18.299
elevated against those two viruses, it appears that we can make

0:31:18.299,0:31:21.559
a significant difference in these patients' physical

0:31:21.559,0:31:26.590
and cognitive status, independent of placebo.

0:31:26.590,0:31:29.809
We were not just happy with

0:31:29.809,0:31:34.570
just seeing this and not being able to explain it. We wanted to go beyond that.

0:31:34.570,0:31:37.970
And we have noticed that in patients who received the drug,

0:31:37.970,0:31:42.710
these cells, called neutrophils, increase in a statistical manner,

0:31:42.710,0:31:46.700
that is not seen in the patients who get placebo.

0:31:46.700,0:31:50.210
So something is associated with neutrophils that

0:31:50.210,0:31:55.299
maybe, maybe, (is) one potential explanation of why they get better.

0:31:55.299,0:31:58.710
The other cells that change

0:31:58.710,0:32:03.200
are the monocytes, in this case they go down in the patients who get the drug,

0:32:03.200,0:32:07.500
and not in those who get the placebo. At at the same time,

0:32:07.500,0:32:10.669
we took the serum of these patients, and through a

0:32:10.669,0:32:14.720
technology that is available here at Stanford, and in collaboration

0:32:14.720,0:32:18.909
with our colleagues in the immunology department, we were able to measure

0:32:18.909,0:32:22.529
through this technique that is called Luminex technology, where you can

0:32:22.529,0:32:27.429
measure a hundred cytokines, a hundred analytes, in a single well

0:32:27.429,0:32:31.549
of a single patient at the same time, we were able to measure what we call

0:32:31.549,0:32:33.820
cytokines. Cytokines are molecules

0:32:33.820,0:32:37.290
that the immune system uses to talk from one cell

0:32:37.290,0:32:41.110
to the other. And through this technology we were able to show

0:32:41.110,0:32:45.769
that in those patients at baseline that I show you that they were slightly worse

0:32:45.769,0:32:50.500
for the treatment group, we show that the certain cytokines were higher

0:32:50.500,0:32:53.830
in those who were worse, than in those who were better--initially,

0:32:53.830,0:32:57.720
like IL5 and IL17. And more importantly,

0:32:57.720,0:33:01.169
over time, the patients on the treatment,

0:33:01.169,0:33:04.210
on the Valganciclovir, on the drug, have

0:33:04.210,0:33:07.500
elevation in cytokines that were not seen

0:33:07.500,0:33:10.980
as much in the patient in the placebo. Cytokines like

0:33:10.980,0:33:16.100
IL5, IL17, cytokines that attract neutrophils--the same cell

0:33:16.100,0:33:20.689
that I mentioned to you that is elevated. Or cytokines that had to do

0:33:20.690,0:33:24.330
with monocyte communication, the same cell that I mentioned to you

0:33:24.330,0:33:27.539
that it goes down. And the drug was safe

0:33:27.539,0:33:31.679
during the period of administration. And we concluded then

0:33:31.679,0:33:35.220
that if the patients have high levels of these antibodies against

0:33:35.220,0:33:38.279
HHV-6 and DBV, giving them

0:33:38.279,0:33:41.740
Valganciclovir for six months

0:33:41.740,0:33:45.240
appears to correlate with an improvement in cognitive and physical

0:33:45.240,0:33:48.620
that is independent from placebo and we have

0:33:48.620,0:33:52.510
a mechanism, proposed a mechanism

0:33:52.510,0:33:57.440
through immunomodulation, meaning that sometime the drugs work;

0:33:57.440,0:34:00.940
not necessarily through the fact that they are killing the organism,

0:34:00.940,0:34:05.590
but by the fact that they are making the immune system (go) one direction

0:34:05.590,0:34:08.918
that is beneficial to the patient. So...

0:34:08.918,0:34:11.960
But I want to emphasize two things.

0:34:11.960,0:34:16.699
Not all the patients have those blood markers. So not everybody will be

0:34:16.699,0:34:20.109
in theory a candidate for that intervention. And unfortunately, not

0:34:20.109,0:34:24.848
all the patients with the markers necessarily improve.

0:34:24.849,0:34:27.969
so that let us, or has led us,

0:34:27.969,0:34:31.290
at Stanford to identify what we call

0:34:31.300,0:34:35.440
sub-groups of patients with CFS, those who

0:34:35.440,0:34:38.829
meet that profile of the HSV-6, EBV,

0:34:38.829,0:34:43.210
we have found other patients that have what we call the herpes simplex one

0:34:43.210,0:34:46.349
or two sub-group. Patients who

0:34:46.349,0:34:49.800
absolutely tell you that their CFS worsened

0:34:49.800,0:34:53.149
when their oral herpes, the famous

0:34:53.149,0:34:57.250
fever blisters, the oral blisters, or genital herpes,

0:34:57.250,0:35:00.329
that when those exacerbate,

0:35:00.329,0:35:03.970
and manifest in the way of painful lesions, those patients

0:35:03.970,0:35:07.780
actually, their symptoms get much more worse,

0:35:07.790,0:35:11.000
or that their disease began when they have the outbreak, the first outbreak

0:35:11.000,0:35:14.100
with one of those two viruses. So that's what we have called a

0:35:14.100,0:35:17.349
herpes simplex sub-group. We have had some Brucella

0:35:17.349,0:35:20.940
patients, others with Q fever, like the ones that they

0:35:20.940,0:35:24.890
found in Australia, mycoplasma, chlamydia,

0:35:24.890,0:35:27.570
and we have found patients who have low titers

0:35:27.570,0:35:30.820
against HSV-6, but have very high levels

0:35:30.820,0:35:34.130
of this HSV-6 virus that

0:35:34.130,0:35:38.619
have also clearly been associated with significant fatigue in these patients,

0:35:38.619,0:35:41.859
and those patients are the ones that we call chromosomally

0:35:41.859,0:35:45.420
integrated human herpes virus six. So this is another

0:35:45.420,0:35:49.910
completely different sub-group. And it's a tougher group

0:35:49.910,0:35:54.490
to treat. I'm sure you remember the first patient that I

0:35:54.500,0:35:58.530
told you. The 50 year-old woman who came in 2008

0:35:58.530,0:36:02.760
to see us, with the hope that we could find something,

0:36:02.760,0:36:06.710
and we did all these titers, and they were low, or negative,

0:36:06.710,0:36:10.900
but she's one of the patients who was found to have very high levels

0:36:10.900,0:36:14.800
of the human herpes virus 6 in her blood. She one of the patients

0:36:14.800,0:36:18.510
that we call, that the virus has found at clever way

0:36:18.510,0:36:22.520
to get into the actual genome, into the genetic material

0:36:22.520,0:36:26.900
of her own cells, in a clever way to hide,

0:36:26.100,0:36:30.640
and to perhaps to produce the damage. So the patient that I mentioned to you

0:36:30.640,0:36:35.520
in 2008, we were studying her--and this is a way to measure

0:36:35.520,0:36:39.200
her fatigue and her cognitive abilities.

0:36:39.200,0:36:42.300
Being 100 is being in complete misery.

0:36:42.300,0:36:46.740
It's really being sick. The CDC has done studies with this questionnaire

0:36:46.740,0:36:50.598
for physical and cognitive dysfunction. Most of the CFS patients

0:36:50.599,0:36:53.920
are around 60. Being completely well

0:36:53.920,0:36:57.760
is around 10. So if you are (a) 60, you are really sick.

0:36:57.760,0:37:00.940
She was around (an) 80. This is the same woman,

0:37:00.940,0:37:05.609
patient, wife, mother, that I talked to you at the beginning.

0:37:05.609,0:37:09.890
We started with the antiviral, and you can see how

0:37:09.890,0:37:13.150
by different antivirual interventions of certain kinds,

0:37:13.150,0:37:16.599
finally she has some relief here. Where

0:37:16.599,0:37:19.670
her level of function going from 80

0:37:19.670,0:37:24.210
to almost 25 is significantly improved.

0:37:24.210,0:37:27.290
She went from not been able to run errands,

0:37:27.290,0:37:31.990
to now go out, and travel, and enjoy the graduation of her

0:37:31.990,0:37:35.959
daughter, et cetera, et cetera. However, those drugs,

0:37:35.960,0:37:39.000
for us to be able to achieve this resolution

0:37:39.000,0:37:42.640
we had to give them at very high doses, and you can only go

0:37:42.640,0:37:46.859
with this drug so long. So we have to move her to other medications that are not

0:37:46.859,0:37:47.640
so effective.

0:37:47.640,0:37:51.250
And unfortunately she has relapsed recently.

0:37:51.250,0:37:55.740
For her, we're going to try hopefully a clever way

0:37:55.740,0:37:59.310
to measure what is in her blood that changes that makes her feel

0:37:59.310,0:38:02.660
so much better, going from 80 which is

0:38:02.660,0:38:06.240
near hell, to around 20 which is near

0:38:06.240,0:38:09.490
health. So hopefully we'll be able to

0:38:09.490,0:38:13.649
achieve that, but I just want to show you this as an example

0:38:13.650,0:38:17.339
that there is something there that we can improve.

0:38:17.339,0:38:20.940
All we have to do is devote resources and more people

0:38:20.940,0:38:24.430
to be able to unveil this mystery.

0:38:24.430,0:38:27.759
So that has been, so far, our experience.

0:38:27.760,0:38:31.760
I would like to mention two things quickly because I'm sure you have

0:38:31.760,0:38:33.500
questions about it.

0:38:33.500,0:38:36.810
It is what recently has been reported as the famous

0:38:36.810,0:38:40.560
XMRV virus. The XMRV virus

0:38:40.560,0:38:44.770
was--that, and the Lancet study about degraded

0:38:44.770,0:38:47.890
exercise. So I'm going to comment on those two things, because they are very

0:38:47.890,0:38:52.420
timely. So the XMRV is a virus that was found

0:38:52.420,0:38:56.480
in prostatic tumors, and it was thought that it could be associated with

0:38:56.480,0:39:00.750
prostatic cancer. But then the surprise came in 2009

0:39:00.750,0:39:04.550
when it was reported by a group from Nevada that patients with

0:39:04.550,0:39:10.490
the disease had 70 percent--it's 67 percent, but you can't remember a 70 percent--

0:39:10.490,0:39:14.720
the CFS patient had the virus. Well yes, only four percent

0:39:14.720,0:39:18.310
of healthy controls had it. So that caused a major splash

0:39:18.310,0:39:21.570
and hope of the possibility that this agent

0:39:21.570,0:39:25.470
could be behind, also, in addition to the other ones that I showed you,

0:39:25.470,0:39:29.629
and in addition to the ones that we are going after at Stanford.

0:39:29.630,0:39:33.700
The problem has been, that following that study,

0:39:33.700,0:39:37.109
there have been two others supporting those findings

0:39:37.109,0:39:41.600
and about six others that show that the association

0:39:41.600,0:39:47.359
is not there. So there is one, this is one study from the U.S., the 70 percent

0:39:47.359,0:39:50.730
versus the four percent that I mentioned to you

0:39:50.730,0:39:55.630
that have the 70 percent in the patients versus four percent in the controls.

0:39:55.630,0:39:59.119
The other study that was positive is a study from Boston

0:39:59.119,0:40:03.420
when it was not 70 percent, it was almost 87 percent,

0:40:03.420,0:40:06.520
and in controls it was about 7 percent.

0:40:06.520,0:40:10.509
All the other studies, all the studies in Europe have been negative;

0:40:10.510,0:40:15.210
the other studies, other than those two in the United States, have been negative,

0:40:15.210,0:40:21.329
except one small one that has not been fully reported that was also positive from New York City.

0:40:21.329,0:40:25.450
so it is a mystery, it's a challenge, it's a controversy,

0:40:25.450,0:40:28.649
and we just have to step up to the challenge and solve it

0:40:28.650,0:40:33.500
for the patients and not shy away and not take a position

0:40:33.500,0:40:36.970
he has been really disappointing to me to see how

0:40:36.970,0:40:40.930
colleagues who do not find the same thing that others do

0:40:40.930,0:40:44.910
step up to the podium and said, "The other findings are wrong;

0:40:44.910,0:40:49.200
we find the truth," et cetera. We are not going to be able able to solve this disease

0:40:49.200,0:40:53.390
through taking dogmatic positions like this. So it is controversial

0:40:53.390,0:40:56.910
but no group has produced proof

0:40:56.910,0:41:01.180
that the association is there; nor any group has produced proof

0:41:01.180,0:41:06.210
that it's not there. The retroviruses--this is a retrovirus--

0:41:06.210,0:41:09.839
they have a great capacity to hide and to do

0:41:09.839,0:41:13.910
bad things, either in a long period of range

0:41:13.910,0:41:17.700
or very short. It's the same group with the HIV virus

0:41:17.700,0:41:21.210
but it's not HIV. A kind of

0:41:21.210,0:41:25.500
unique life cycle where they can get very cleverly

0:41:25.500,0:41:28.960
inside the cell and they can integrate into the human

0:41:28.960,0:41:32.000
genetic material, hence their ability to hide

0:41:32.000,0:41:35.700
and to cause, in a very sneaky way,

0:41:35.700,0:41:39.359
disease (in) us. There are several kinds;

0:41:39.359,0:41:44.600
this XMRV virus came from mice--no question about it--

0:41:44.600,0:41:48.890
and some of those viruses have mutated to the point that they are only

0:41:48.890,0:41:49.819
able to stay in humans;

0:41:49.819,0:41:53.190
there are others that can be in mice and humans,

0:41:53.190,0:41:57.109
and there are others that cannot be in humans. So there are different kinds,

0:41:57.109,0:42:00.609
but the reality is that the question is out there

0:42:00.609,0:42:04.339
and it needs to be solved. And we as America

0:42:04.339,0:42:07.640
and the scientific community need to step up and

0:42:07.640,0:42:12.569
solve the mystery. There are different ways to measure the virus, so that's

0:42:12.569,0:42:16.740
possibly part of the problem. There are ways to measure the actual virus;

0:42:16.740,0:42:20.848
with measuring the nuclear acid to look at the proteins,

0:42:20.849,0:42:23.990
to look at the cultural dividers, to look at

0:42:23.990,0:42:29.740
how the antibody responds in humans to the virus, as a way to detect the virus--

0:42:29.740,0:42:33.439
So there are different methods that make it a little bit more difficult, but not

0:42:33.440,0:42:37.530
impossible, to understand what is happening. Also,

0:42:37.530,0:42:40.890
people, or different laboratories, using different

0:42:40.890,0:42:44.348
reagents; they use different

0:42:44.349,0:42:49.329
positive or negative controls; the virus appears to be in very small amounts,

0:42:49.329,0:42:52.990
so that makes it hard for people to find it.

0:42:52.990,0:42:57.959
And also, the studies come from different geographical areas.

0:42:57.960,0:43:01.100
Infectious diseases is characterized by this.

0:43:01.100,0:43:05.900
There are infections that present only in the United States and ever seen in Europe.

0:43:05.900,0:43:10.569
There are infections that are only seen in Latin America, never seen outside

0:43:10.569,0:43:14.170
the Americas. So this is not news--

0:43:14.170,0:43:17.290
that an infectious agent could be restricted to certain geographical

0:43:17.290,0:43:21.890
locales, and it could be the case in this situation as well.

0:43:21.890,0:43:25.200
So what is the bottom line? What is the bottom line with this

0:43:25.200,0:43:28.609
XMRV virus? It can be present

0:43:28.609,0:43:33.310
in people who have no disease. And it could be, according to the study so far

0:43:33.310,0:43:37.650
up to seven percent. It can be present in patients with prostate cancer:

0:43:37.650,0:43:41.750
up to 27 percent. It can can be present in patients with CFS:

0:43:41.750,0:43:47.230
up to 87 percent. All the European studies have been negative so far.

0:43:47.230,0:43:51.390
In the study from Boston, there were patients who were positive

0:43:51.390,0:43:54.480
in blood samples that had been taken fifty years

0:43:54.480,0:43:58.390
ago--they went to those patients again, they got blood again, and they were

0:43:58.390,0:43:59.710
positive again.

0:43:59.710,0:44:02.780
so we know that the virus can be there

0:44:02.780,0:44:06.890
for long periods of time. And obviously

0:44:06.890,0:44:09.520
we need to have the right studies

0:44:09.520,0:44:13.670
in a smart way and we are fortunate, the Stanford group is fortunate,

0:44:13.670,0:44:18.000
to be associated now with a group at Columbia

0:44:18.000,0:44:22.990
with directions, and the directions of the NIH, to hopefully be able

0:44:22.990,0:44:25.220
to provide the right kind of data that will help

0:44:25.220,0:44:29.578
to support one way or the other. And another possibility

0:44:29.579,0:44:34.130
is to do a specific intervention, because the drugs that work against a virus

0:44:34.130,0:44:38.490
are very specific. In the next few minutes,

0:44:38.490,0:44:44.149
I would like to share with you how at Stanford we have tried to put this together

0:44:44.150,0:44:47.680
as a model of pathogenesis of this disease.

0:44:47.680,0:44:52.180
So as I told you before, it is known that some patients start with infection

0:44:52.180,0:44:55.440
and that the more severe the infection at the beginning,

0:44:55.440,0:44:59.290
the higher is the chance that they go into chronic fatigue syndrome.

0:44:59.290,0:45:03.690
Most of the infections that have associated with

0:45:03.690,0:45:07.180
chronic fatigue syndrome are intracellular: they hide

0:45:07.180,0:45:11.328
inside the cell. They like to go to the brain;

0:45:11.329,0:45:15.230
they like to go to the lymph nodes. So I think that they are telling us something

0:45:15.230,0:45:19.390
there from a mechanistic point of view. Several

0:45:19.390,0:45:22.720
infections can do the same thing; they can

0:45:22.720,0:45:26.189
trigger CFS. I think that this is telling us

0:45:26.190,0:45:29.190
that what is most likely responsible for

0:45:29.190,0:45:33.490
the problem it's not the organism itself attacking the patient, but it's the

0:45:33.490,0:45:35.980
immune response to them.

0:45:35.990,0:45:38.500
Several of them can do it; the severe ones seem to be

0:45:38.500,0:45:43.140
doing it more successfully, so it's likely that is the immune response against them

0:45:43.140,0:45:46.339
what is doing it. It's possible

0:45:46.339,0:45:49.900
that it is doing it because they all share something in common

0:45:49.900,0:45:53.000
that triggers the same immune response that is damaging

0:45:53.000,0:45:56.810
or that they00:02:18,150 --> 00:02:21,330[br]for 23 years.

0:02:21.330,0:02:24.940
Twenty-three years. She had a wonderful life;

0:02:24.940,0:02:28.780
she has a supporting and loving husband--

0:02:28.780,0:02:32.319
still he's with her--who works for a high-tech company,

0:02:32.319,0:02:37.470
two super children, enjoy her full-time jobs as a sales manager

0:02:37.470,0:02:42.450
and as a housemaker. Being a housewife or a housemaker, as you know, is

0:02:42.450,0:02:43.950
a full-time job on its own.

0:02:43.950,0:02:48.738
She had two full-time jobs. And she was the source of constant joy

0:02:48.739,0:02:53.120
for her family and friends. She had probably achieved what many will call the

0:02:53.120,0:02:54.900
"American Dream."

0:02:54.900,0:02:57.879
In 1985, that dream came to a stop.

0:02:57.879,0:03:02.140
At the age of 30, and after giving birth to her first child,

0:03:02.140,0:03:06.679
she developed fatigue--fatigue that became worse over the

0:03:06.680,0:03:10.340
next 23 years, becoming disabling

0:03:10.340,0:03:14.100
in 2003. She can only do 30

0:03:14.100,0:03:17.329
percent of what she was capable of doing before she fell ill.

0:03:17.330,0:03:20.730
Even running small errands, like going to grocery

0:03:20.730,0:03:25.230
shopping, has become a major ordeal. Here we have

0:03:25.230,0:03:28.768
a life that has come to a standstill:

0:03:28.769,0:03:33.610
Thirty percent of what she's capable of doing for 23 years.

0:03:33.610,0:03:38.209
So I want you to carefully weigh everything that is being presented to you; this is

0:03:38.209,0:03:39.430
a real case.

0:03:39.430,0:03:43.120
So how is it possible to live with a disease

0:03:43.120,0:03:47.129
that makes you be thirty percent of who you are, and still

0:03:47.129,0:03:50.409
be able to live with that for 23 years?

0:03:50.409,0:03:53.579
In addition to that primary, persistant

0:03:53.580,0:03:56.939
fatigue, she develops other worrisome symptoms:

0:03:56.939,0:04:00.870
Brain fog. It's not uncommon for patients to tell you

0:04:00.870,0:04:06.300
they have brain fog. And it's expressed by significant cognitive impairment--

0:04:06.300,0:04:11.430
all the way to 30 percent. So 70 percent of her brain function

0:04:11.430,0:04:14.459
was taken, or has been taken, by her illness.

0:04:14.459,0:04:20.250
mental tasks leave her fatigued; compiling information became extremely difficult;

0:04:20.250,0:04:25.330
she feels jumbled and confused. She in addition has had headaches,

0:04:25.330,0:04:28.960
cough, sore throats, unrefreshing sleep.

0:04:28.960,0:04:32.210
She wakes up in the morning as if she would have not slept--

0:04:32.210,0:04:35.710
she had not slept the night before--with the same level

0:04:35.710,0:04:41.390
of tiredness as when she bed. Post-exertional malaise.

0:04:41.400,0:04:46.540
Not many diseases--and I see respectable physicians here in the audience--

0:04:46.540,0:04:51.320
not many diseases will give you what the patients with chronic fatigue syndrome

0:04:51.320,0:04:52.330
experience

0:04:52.330,0:04:56.650
when they overdo it. And overdoing it can be just running a small errand.

0:04:56.650,0:05:00.710
Overdoing can be walking a mile. But after that

0:05:00.710,0:05:04.000
level of exercise, or that level

0:05:04.000,0:05:07.889
of, of putting the body through that stress--and it could be mental,

0:05:07.889,0:05:11.440
could be emotional, cognitive

0:05:11.440,0:05:14.680
or physical--they go into a crash

0:05:14.680,0:05:18.380
period. It's not the physical

0:05:18.380,0:05:21.630
sort of strain that you experience when you go and run

0:05:21.630,0:05:25.639
a whole mountain, around miles when you are healthy, your feel tired afterwards

0:05:25.639,0:05:26.370
but you have the

0:05:26.370,0:05:29.690
endorphin kick that makes you feel good because you did a lot of

0:05:29.690,0:05:33.160
exercise or physical activity. It is not that.

0:05:33.160,0:05:37.110
It's a crash where the patient feels sick, many times with the feeling

0:05:37.110,0:05:40.180
of having a flu. In addition to

0:05:40.180,0:05:44.330
post-exertional malaise, she feels muscle pain,

0:05:44.330,0:05:48.440
joint pain. Her primary care provider

0:05:48.440,0:05:52.560
is arguably one of the best internists in the Bay Area.

0:05:52.560,0:05:57.360
And she has been fortunate to have him, because he has been there for her

0:05:57.360,0:06:01.680
for all this period, being sure she doesn't have a cancer,

0:06:01.680,0:06:05.270
low thyroid, a rheumatological disease--

0:06:05.270,0:06:10.130
he has been so careful in being sure that we don't treat her as (having) chronic fatigue syndrome

0:06:10.130,0:06:13.990
when in fact she could have had something else that can be put in a box,

0:06:13.990,0:06:18.539
and it can be treated from, you know, day one to day X.

0:06:18.539,0:06:22.289
And, most importantly, he believes that her

0:06:22.289,0:06:26.370
illness is real. I cannot tell you that--

0:06:26.370,0:06:30.900
--whatever we are doing at Stanford that may have worked, and we are

0:06:30.900,0:06:34.720
pleased with those results, may have worked for some patients--

0:06:34.720,0:06:38.169
it could be still (up) for debate. We still have to do a lot of more work

0:06:38.169,0:06:38.789
to understand

0:06:38.789,0:06:41.900
what are we doing to the patients, that some of them have

0:06:41.900,0:06:46.698
gotten better. But the one thing: a hundred percent of--and not all of the

0:06:46.699,0:06:48.330
patients get better, unfortunately--

0:06:48.330,0:06:51.340
--but the one thing that I can tell you, that a hundred percent of the patients

0:06:51.340,0:06:52.530
are grateful,

0:06:52.530,0:06:56.490
is when we tell them, "You have a real disease."

0:06:56.500,0:06:59.990
And they break down there. Because for the first time they find somebody in the

0:06:59.990,0:07:01.740
medical community

0:07:01.740,0:07:05.990
telling them, "You are not lying, you are not faking, you are not malingering;

0:07:05.990,0:07:09.940
you have a disease you have no control on."

0:07:09.940,0:07:14.219
And then, then they feel at least validated. So it's very important for--

0:07:14.220,0:07:18.849
hopefully, one day, my dream is that our medical community

0:07:18.849,0:07:22.830
will produce a formal apology to the patients

0:07:22.830,0:07:26.280
for not having believed them all these years, that they were facing

0:07:26.280,0:07:31.309
a real illness. It's true that currently we don't have a single way

0:07:31.310,0:07:34.610
to determine that somebody has CFS in an objective way.

0:07:34.610,0:07:37.660
It's true that we don't have a single treatment, but

0:07:37.660,0:07:41.840
the patients do have a real disease.

0:07:41.840,0:07:44.948
The fact that the patients give you so much

0:07:44.949,0:07:48.940
history of suffering, and that is incapacitating,

0:07:48.940,0:07:53.160
that when you try to look for objective signs that

0:07:53.160,0:07:58.300
that, that correlates with what they are telling you--that dichotomy between

0:07:58.300,0:08:01.330
they telling you, "I am so sick, I cannot

0:08:01.330,0:08:04.780
even leave the house." But then when you do testing,

0:08:04.780,0:08:08.680
when you examine them, you do not find anything that is

0:08:08.690,0:08:11.810
palpable or tangile, that is not new.

0:08:11.810,0:08:15.759
Even back in the 1900s, when physicians

0:08:15.759,0:08:19.340
who had this special skill

0:08:19.340,0:08:24.200
for having, for finding diseases in the physical exam, like William Osler

0:08:24.200,0:08:28.620
famously said, "In all forms there is a striking lack of accordance

0:08:28.620,0:08:32.140
between the symptoms of which the patients complain and the objective

0:08:32.140,0:08:36.990
changes discoverable by the physician." So it has been more than two hundred years that

0:08:36.990,0:08:42.760
that discordance is known, but what is sad is that it has been equated

0:08:42.760,0:08:46.339
to the patient has something that is in their head, something that they have

0:08:46.339,0:08:50.250
control, just with their minds. So CFS

0:08:50.250,0:08:53.830
is a real disease. It's experienced by

0:08:53.830,0:08:59.620
one to four million Americans, perhaps 17 or more million people (it's worldwide);

0:08:59.620,0:09:04.459
there are no diagnostic tests that can identify with certainty

0:09:04.459,0:09:09.199
the patient. Pneumonia: pneumonia, for example,

0:09:09.200,0:09:12.360
is an infection. And when a patient has cough,

0:09:12.360,0:09:15.899
and fever, and tired, and sore throat,

0:09:15.899,0:09:19.209
we do a chest X-ray and we see something. We see

0:09:19.209,0:09:23.699
a shadow in that chest X-ray, and we say the patient has pneumonia.

0:09:23.700,0:09:27.790
We don't have the equivalent to that shadow in CFS.

0:09:27.790,0:09:31.899
We desperately need that, and this is one of the goals that we have set

0:09:31.899,0:09:35.980
our group at Stanford, is to one day be able to tell our patients,

0:09:35.980,0:09:40.230
"Yes, you have a shadow in your chest X-ray, CFS disease,

0:09:40.230,0:09:43.810
and yes, that validates you. There are no

0:09:43.810,0:09:46.890
definitive treatments, and I'll tell you the

0:09:46.890,0:09:50.890
small progress that we have made at Stanford with some groups of patients in

0:09:50.890,0:09:51.959
this regard,

0:09:51.959,0:09:55.290
and it's true that some patients spontaneously improve,

0:09:55.290,0:10:00.579
but after a certain period of time, their rate of improvement really is small.

0:10:00.580,0:10:04.440
It could be as high as seventy, eighty percent

0:10:04.440,0:10:09.190
in the first year of disease, but it becomes really much lower

0:10:09.190,0:10:12.870
as the years come (pass).

0:10:12.870,0:10:16.950
So what makes CFS such a difficult challenge?

0:10:16.950,0:10:20.990
We have, of course, compassionate colleagues and

0:10:20.990,0:10:24.459
people who are extremely smart in our schools and

0:10:24.459,0:10:27.859
in offices, but what makes it so hard

0:10:27.860,0:10:31.690
not to see it many times as a real disease, for one side,

0:10:31.690,0:10:35.930
is the fact that there are so many symptoms coming from so many angles.

0:10:35.930,0:10:40.290
We physicians have this thinking that if you give us a symptom,

0:10:40.290,0:10:43.310
we try to look for what organ it's coming from.

0:10:43.310,0:10:46.790
So the cough could be coming from the lungs,

0:10:46.790,0:10:51.560
from the heart, from a medication, occasionally from some area of the brain,

0:10:51.560,0:10:55.420
so we start to see where the organ that is involved.

0:10:55.420,0:10:58.550
And many times the symptoms sort of like,

0:10:58.550,0:11:02.670
are [related] to a single system, to an organ, but when the patient

0:11:02.670,0:11:07.180
gives you, with validity, the symptoms coming from so many organs:

0:11:07.180,0:11:10.349
muscle pain, joint pain, brain fog,

0:11:10.350,0:11:14.899
fatigue, et cetera, then it's hard for a physician to take,

0:11:14.899,0:11:18.649
"What do I do with this?" So it's the constellation,

0:11:18.649,0:11:22.430
it's the complexity, it's the fact that they are so hetereogeneous

0:11:22.430,0:11:26.510
that has made this disease difficult to deal with.

0:11:26.510,0:11:29.680
And things will only get worse when we have

0:11:29.680,0:11:33.479
health care systems that only allow physicians for the first visit

0:11:33.480,0:11:37.680
45 minutes or 60 minutes, and for follow-up, 15 minutes or 20 minutes.

0:11:37.680,0:11:38.459
That's going to get

0:11:38.459,0:11:42.250
only worse. The disease is disabling,

0:11:42.250,0:11:46.589
the combination of symptoms--not only is the fatigue the central core

0:11:46.589,0:11:50.519
of the symptom, but what I refer to you as brain fog.

0:11:50.519,0:11:53.950
Unfortunately, the name "chronic fatigue syndrome"

0:11:53.950,0:11:57.589
has not served well the disease or the patients.

0:11:57.589,0:12:01.000
There are other symptoms. It's not just the fatigue.

0:12:01.000,0:12:04.850
And the most and the recognized symptom in patients with chronic fatigue

0:12:04.850,0:12:07.000
syndrome is the cognitive impairment.

0:12:07.000,0:12:11.339
It is real. It is there. It incapacitates patients.

0:12:11.339,0:12:14.380
Patients say that they have difficulty concentrating,

0:12:14.380,0:12:18.230
finding words; they cannot produce the same level

0:12:18.230,0:12:21.230
of executive function that they used to exercise,

0:12:21.230,0:12:24.540
and they cannot sustain those activities for much.

0:12:24.540,0:12:29.120
They also have sleep problems and pains in the joints and muscles.

0:12:29.120,0:12:33.200
They usually have the disease for six months or longer.

0:12:33.200,0:12:37.610
So we are trying to differentiate those situations where you get the fatigue

0:12:37.610,0:12:41.490
and fortunately it goes away

0:12:41.490,0:12:45.860
within a short period of time. So it has generally been agreed upon

0:12:45.860,0:12:49.820
that if you have the fatigue for more than six months is when you have to worry

0:12:49.820,0:12:53.190
about the possibility that initial illness

0:12:53.190,0:12:56.470
could have been the beginning of the nightmare

0:12:56.470,0:13:00.160
that will ensue months or years later.

0:13:00.160,0:13:03.920
Many patients--many patients will tell you

0:13:03.920,0:13:07.240
that their nightmare began with a

0:13:07.240,0:13:10.389
viral-like illness. They will tell you that. They are--

0:13:10.389,0:13:13.930
you know, the way I see this disease is that,

0:13:13.930,0:13:18.469
it is speaking to us. It is telling us the clue--it's giving us the clues,

0:13:18.470,0:13:21.649
we just have not had the patience

0:13:21.649,0:13:24.980
and the time

0:13:24.980,0:13:28.000
to really listen to the clues that the disease is giving us there.

0:13:28.000,0:13:31.350
But they tell us, "I was totally fine."

0:13:31.350,0:13:35.220
And they give you the month. Sometimes they give you the date,

0:13:35.220,0:13:38.490
the day of the month, and the year, when their whole

0:13:38.490,0:13:42.600
life crumbled, like the patient that I illustrated to you.

0:13:42.600,0:13:47.240
It is important, however, every time that somebody says that they have

0:13:47.240,0:13:47.949
chronic fatigue syndrome,

0:13:47.949,0:13:51.760
that we rule out other potential explanations

0:13:51.760,0:13:55.370
that are more circumscribed to a single

0:13:55.370,0:14:00.880
ideology or cause that can be fixed relatively quick.

0:14:00.880,0:14:04.709
This is this study that validates what the patients have been telling us

0:14:04.709,0:14:08.239
all along. This is a study that was done in Australia,

0:14:08.240,0:14:12.649
where they have the capacity and resources, that as soon as somebody gets

0:14:12.649,0:14:14.500
diagnosed with acute

0:14:14.500,0:14:18.720
infectious mononucleosis, or Epstein-Barr virus infection,

0:14:18.720,0:14:22.250
or another infection that they have common in Australia called

0:14:22.250,0:14:25.290
Q fever. Q fever can go into the lungs,

0:14:25.290,0:14:29.939
can go into the heart. It's called Q fever, caused by an organism called

0:14:29.940,0:14:31.649
Coxiella burnetii.

0:14:31.649,0:14:35.610
Or another infection they call Ross River virus.

0:14:35.610,0:14:39.790
For the purposes of this conversation, these physicians in Australia have the

0:14:39.790,0:14:40.990
capacity

0:14:40.990,0:14:45.149
to register and capture patients who have been dianogised

0:14:45.149,0:14:48.320
with acute infection of any of those three

0:14:48.320,0:14:51.699
kinds: either infectious mononucleosis,

0:14:51.699,0:14:54.939
Q fever, or the Ross River virus.

0:14:54.940,0:14:58.889
And to their surprise, the people who,

0:14:58.889,0:15:02.610
the patients who were followed over time prospectively--

0:15:02.610,0:15:06.310
and this is the participants that remain

0:15:06.310,0:15:09.899
having fatigue after the acute infection

0:15:09.899,0:15:13.790
was diagnosed here--so in the, in the

0:15:13.790,0:15:16.949
X axis . . . you can follow

0:15:16.949,0:15:21.250
the time after acute infection, six months, twelve months after,

0:15:21.250,0:15:25.149
and here in the . . . Y axis,

0:15:25.149,0:15:29.600
you can see the patients who have fatigue, and you can see obviously patients

0:15:29.600,0:15:30.459
getting better,

0:15:30.459,0:15:34.149
and less having fatigue, but look at the proportion of cases

0:15:34.149,0:15:39.540
that remain fatigued after 12 months. And they follow those patients later;

0:15:39.540,0:15:42.759
Eleven percent of the patients

0:15:42.759,0:15:46.680
develop chronic fatigue syndrome after these acute

0:15:46.680,0:15:50.219
infections. Our patients were telling us that

0:15:50.220,0:15:55.680
all along. And a study had to be done to prove that they were right.

0:15:55.680,0:15:59.420
So it looks like at least in some cases of CFS

0:15:59.420,0:16:03.149
there is an infectious insult at the beginning

0:16:03.149,0:16:06.980
of the illness. Whether it's the infectious agent per se

0:16:06.980,0:16:10.870
or the immune response against that agent, what (affects) it that much

0:16:10.870,0:16:14.829
is unknown at this time. But hopefully one day we'll be able

0:16:14.829,0:16:18.130
to solve that puzzle.

0:16:18.130,0:16:21.509
This is another study done in the United States

0:16:21.509,0:16:25.910
Similar idea. These are other lessons--these are kids.

0:16:25.910,0:16:30.959
They have also been able to capture them at the time they had the acute infection

0:16:30.959,0:16:34.508
and they find that about four percent after

0:16:34.509,0:16:39.240
24 months--four percent--they have had but they have met the criteria

0:16:39.240,0:16:42.769
of chronic fatigue syndrome. So clearly

0:16:42.769,0:16:45.920
there is now proof

0:16:45.920,0:16:50.600
that a patient can go into this mysterious disease, an illness,

0:16:50.600,0:16:53.170
after they have had an acute infection. And

0:16:53.170,0:16:56.509
please note that many of those infections

0:16:56.509,0:17:00.220
also have what we call an asymptomatic phase. In other words,

0:17:00.220,0:17:05.890
people, patients, can get those infections, and not have symptoms.

0:17:05.890,0:17:08.208
What they have found is that in general,

0:17:08.209,0:17:13.750
the more acute, severely ill the patients are, the more severe the disease is

0:17:13.750,0:17:17.348
at the time when they have developed for the first time,

0:17:17.348,0:17:23.539
the higher is the likelihood that they will go into chronic fatigue syndrome.

0:17:23.539,0:17:28.600
So it is really important, and this is just to make one point--

0:17:28.600,0:17:31.719
is that before we declare someone

0:17:31.720,0:17:36.890
as having chronic fatigue syndrome, not only that six months have passed,

0:17:36.890,0:17:40.620
for now--maybe in the future we will learn to identify

0:17:40.620,0:17:43.789
those who will go into chronic fatigue syndrome very early so we can

0:17:43.789,0:17:45.600
intervene early--but for now,

0:17:45.600,0:17:48.709
the only way we can do it is by waiting. We don't have a way to

0:17:48.710,0:17:49.490
distinguish those

0:17:49.490,0:17:53.340
except that you can say, the more severe cases perhaps, you will have to pay more

0:17:53.340,0:17:54.830
attention to them.

0:17:54.830,0:17:58.899
But it's important that a very good internist, primary care provider,

0:17:58.900,0:18:02.910
family medicine physician, does a comprehensive

0:18:02.910,0:18:06.200
job looking for alternative explanations--

0:18:06.200,0:18:09.129
psychiatric, psychologic, neurological--

0:18:09.130,0:18:13.160
Because those can be relatively easily fixed. Be sure that we don't have a

0:18:13.160,0:18:14.929
cancer that has not been diagnosed

0:18:14.929,0:18:18.140
that is causing the fatigue, that is not a low thyroid,

0:18:18.140,0:18:21.830
hormone production. Once that has been done,

0:18:21.830,0:18:25.850
then we look at patients who have had the fatigue for more than six months

0:18:25.850,0:18:30.230
and who have other symptoms. Unfortunately, there is no other way

0:18:30.230,0:18:33.789
to do it. We don't have that shadow in the chest X-ray

0:18:33.789,0:18:36.940
that (lets) you see pneumonia--yet. And

0:18:36.940,0:18:40.260
We couple the fatigue that has lasted for six months

0:18:40.260,0:18:45.270
plus four of any of this impaired concentration of the brain fog,

0:18:45.270,0:18:48.299
sore throat, lymph nodes that are enlarged

0:18:48.299,0:18:51.330
and painful, muscle pain, joint pain,

0:18:51.330,0:18:56.270
new headaches, the unrefreshing sleep, and the post-exertional malaise.

0:18:56.270,0:18:59.490
They are often with symptoms of depression.

0:18:59.490,0:19:03.640
It's not that the depression causes chronic fatigue syndrome.

0:19:03.640,0:19:07.300
It's that they are depressed because their lives have been been ruined,

0:19:07.300,0:19:10.639
their life has been taken away, and they want that life back

0:19:10.640,0:19:14.610
and they cannot have it. So it is unfortunate that

0:19:14.610,0:19:17.879
we tend to see the periphery and not see how

0:19:17.880,0:19:21.650
it evolved. Clinically,

0:19:21.650,0:19:25.900
those patients, their fatigue is not

0:19:25.900,0:19:28.350
alleviated by resting,

0:19:28.350,0:19:32.439
and it's not the result of, because they are doing something

0:19:32.440,0:19:36.630
something and they are not stopping. And in many cases,

0:19:36.630,0:19:39.950
they lose their previous levels of occupational,

0:19:39.950,0:19:43.470
educational, social, or personal activities.

0:19:43.470,0:19:47.320
It's very important to note that many of them

0:19:47.320,0:19:51.129
give you neurological symptoms

0:19:51.130,0:19:54.320
that are hard to put in any category.

0:19:54.320,0:19:58.580
At a meeting we were participating last night

0:19:58.580,0:20:02.260
in, in the Washington area, we were sitting with

0:20:02.260,0:20:06.870
neurologists and other physicians, and it became very clear

0:20:06.870,0:20:10.490
that everybody's seeing the same thing.

0:20:10.490,0:20:13.330
Not only the fatigue, not only the brain fog,

0:20:13.330,0:20:18.100
but these funny tremors, twitches, that we call

0:20:18.100,0:20:22.250
myoclonus fasciculations, things that normally will trigger the possibility of a

0:20:22.250,0:20:23.169
neurlogical disease--

0:20:23.169,0:20:27.230
these patients are having something in that area.

0:20:27.230,0:20:31.390
so again, it seems like the disease is speaking to us

0:20:31.390,0:20:35.450
in soft tones, and we're just not able to listen to it

0:20:35.450,0:20:39.419
in a careful way. So it is a real disease,

0:20:39.419,0:20:43.100
but it's an infectious, it is immunological,

0:20:43.100,0:20:47.289
it's endocrine, neurological, cardiac, psychiatric,

0:20:47.289,0:20:50.480
and so everybody seems to be looking at it from the wrong angle

0:20:50.480,0:20:53.820
depending on what their area is. And

0:20:53.820,0:20:57.350
hopefully one day will be able to see it three hundred and sixty

0:20:57.350,0:21:01.719
to be able to comprehend better what is really is, what it's doing--

0:21:01.720,0:21:05.690
the disease to these patients. And part of the problem

0:21:05.690,0:21:10.150
is that, as I said, it's a constellation of systems, so it's a systemic

0:21:10.150,0:21:15.419
challenge; it lasts! It can go on for decades.

0:21:15.419,0:21:20.190
Is it possible that the CFS that one patient has is different than the other?

0:21:20.190,0:21:21.809
Of course it could be possible.

0:21:21.809,0:21:25.639
Like in pneumonia, you have this same shadow in two patients

0:21:25.640,0:21:28.730
but it's caused by a different organism.

0:21:28.730,0:21:32.490
So when you study CFS patients in the air, in general,

0:21:32.490,0:21:36.380
it could be that you are studying different subgroups, and as you try to

0:21:36.380,0:21:37.409
make it a one,

0:21:37.409,0:21:41.159
your findings could be diluted for that reason.

0:21:41.159,0:21:44.390
Also is very likely that the disease evolves.

0:21:44.390,0:21:47.980
It changes. The patient who has illness for less than a year

0:21:47.980,0:21:52.900
possibly will have a different kind of test, positive or negative,

0:21:52.900,0:21:58.408
than someone who has had the disease for ten or twenty years.

0:21:58.409,0:22:01.789
I have to bring up this study. Because in

0:22:01.789,0:22:05.640
our infectious diseases community--so I told you that many patients tell you

0:22:05.640,0:22:07.210
that there is an

0:22:07.210,0:22:11.270
infection at the beginning of the illness--this is this study that has been

0:22:11.270,0:22:16.940
cited as a study that shows that an anti-microbial intervention

0:22:16.940,0:22:20.570
does not work for patients with chronic fatigue syndrome. It was a study that was

0:22:20.570,0:22:22.129
published in the late 80s,

0:22:22.130,0:22:27.940
where they took 27 patients. They had high titers against Epstein-Barr virus

0:22:27.940,0:22:31.230
virus; they had been ill for at least seven years;

0:22:31.230,0:22:34.610
and they gave those patients acyclovir for thirty

0:22:34.610,0:22:37.908
days. So they got IV for seven days,

0:22:37.909,0:22:41.250
and oral for thirty days. So no more

0:45:56.810,0:46:00.730
similar mechanisms of damaging, or immunopathology,

0:46:00.730,0:46:07.140
as also is known. The fact that the disease can be pressing for so many years

0:46:07.140,0:46:10.598
is telling us something. It's whispering to us something.

0:46:10.599,0:46:14.810
The fact that somebody could have a disease and not die of it

0:46:14.810,0:46:19.109
for so long is giving us clues of the mechanism.

0:46:19.109,0:46:22.339
If it's an infection that is doing it, it will mean

0:46:22.339,0:46:26.390
that the infectious agent is capable of coming out of the hiding place

0:46:26.390,0:46:31.400
at a low level. And the immune system attacks the infection,

0:46:31.400,0:46:34.290
successfully puts that pathogen back in the hiding place,

0:46:34.290,0:46:37.859
but it's the same immune response perhaps that is making the patients sick.

0:46:37.859,0:46:41.670
Ad it just perpetuates the cycle. The patients tell us,

0:46:41.670,0:46:45.450
they had been telling us for years,

0:46:45.450,0:46:49.399
"I get this fluctuating level(s) of disease."

0:46:49.400,0:46:53.240
And I think the immune system is acting as a double-edged sword;

0:46:53.240,0:46:57.290
it's putting that organism back in (its) hiding place, but it's making the patient

0:46:57.300,0:46:59.420
possibly sick.

0:46:59.420,0:47:04.290
So the other observation is that most of the patients are women;

0:47:04.290,0:47:07.349
most of them get better during pregnancy

0:47:07.349,0:47:10.640
and most of them get worse after birth.

0:47:10.640,0:47:13.670
Remember that patient that I mentioned to you: that she got the disease

0:47:13.670,0:47:17.170
after the birth of her son. So that suggests

0:47:17.170,0:47:21.540
an autoimmune disease, or an HLA association. Many diseases

0:47:21.540,0:47:24.670
that have been found to be autoimmune had that exact

0:47:24.670,0:47:27.950
same behavior. Lastly,

0:47:27.950,0:47:32.290
I wanna comment to you, comment with you,

0:47:32.300,0:47:35.869
the highly publicized study

0:47:35.869,0:47:39.790
that came out of London where they

0:47:39.790,0:47:42.920
did what is called adaptive pacing therapy,

0:47:42.920,0:47:47.440
cognitive behavior therapy, or graded exercise therapy,

0:47:47.440,0:47:50.960
or simply, a specialized medical care

0:47:50.960,0:47:55.590
for patients with chronic fatigue syndrome. Adaptive pacing therapy

0:47:55.590,0:47:58.550
is to tell the patient, "Do what you feel, but do not

0:47:58.550,0:48:01.780
overdo it. Cognitive behavioral therapy

0:48:01.780,0:48:05.270
is they work with a counselor, with a psychologist,

0:48:05.270,0:48:10.470
to be sure that they overcome the fear of doing things, because they would crash,

0:48:10.470,0:48:13.759
but they also get the same message: avoid the crashes.

0:48:13.760,0:48:16.930
But this time they do it under cognitive

0:48:16.930,0:48:21.400
behavioral intervention. Graded exercise therapy

0:48:21.400,0:48:24.690
is they work with physical therapy individuals

0:48:24.690,0:48:28.880
with the same goal--not to crash--but they do have some kind of

0:48:28.880,0:48:32.440
schedule, graded exercise activity.

0:48:32.440,0:48:36.100
in all the groups, either adaptive pacing therapy,

0:48:36.100,0:48:40.200
cognitive behavior, graded exercise therapy, the main goal was to

0:48:40.200,0:48:43.640
avoid the patient crashing, however the idea

0:48:43.640,0:48:47.348
was to achieve that through these different means that I described to you.

0:48:47.349,0:48:51.490
And a fourth group, a specialist medicare care--

0:48:51.490,0:48:55.459
those patients simply got a good physician who new chronic fatigue syndrome

0:48:55.460,0:48:58.500
but did nothing other than just provide general medical care.

0:48:58.500,0:49:01.710
And this is what was found.

0:49:01.710,0:49:05.809
So. The patients who got the adaptive pacing therapy

0:49:05.809,0:49:09.880
just don't don't crash, trust your instincts--

0:49:09.880,0:49:13.339
basically did not, so, in this score--

0:49:13.339,0:49:16.869
in this score, going down is getting better.

0:49:16.869,0:49:20.380
and really, these patients are really

0:49:20.380,0:49:23.450
Sick. And in this case...

0:49:23.450,0:49:27.790
In this case, it was clearly that the patients did not improve

0:49:27.790,0:49:31.509
by simply telling them, "Trust your instincts."

0:49:31.510,0:49:34.700
The patients who had the cognitive behavioral therapy,

0:49:34.700,0:49:38.430
they actually improved their performance

0:49:38.430,0:49:41.500
but they did not get cured from CFS.

0:49:41.500,0:49:45.250
It is so sad that this study is being cited

0:49:45.250,0:49:48.390
as "cognitive behavorial therapy is curing CFS."

0:49:48.390,0:49:53.660
It's not true. The patients simply got better, and it's good that the patients got better,

0:49:53.660,0:49:57.828
it was statistically significant, but they were far from going back to

0:49:57.829,0:49:59.260
their normal levels.

0:49:59.260,0:50:03.500
The same thing with the graded exercise therapy--they got better

0:50:03.500,0:50:07.650
in a statistically significant manner, but they were far from being completely well.

0:50:07.650,0:50:11.540
And the same thing, the same findings were for the physical

0:50:11.540,0:50:15.940
function in that regard. So that the

0:50:15.940,0:50:19.700
same authors of the papers said, "Our finding that

0:50:19.700,0:50:23.890
(the) study treatments, like those, were only moderately

0:50:23.890,0:50:26.529
effective," they are not saying that they are curing CFS,

0:50:26.530,0:50:32.430
also suggests that researching to more effective treatments are needed

0:50:32.430,0:50:37.569
and that the fact that behavioral intervention means that patients get better

0:50:37.569,0:50:40.680
by no means means that this is psychological in nature.

0:50:40.680,0:50:45.900
And I have to say that, because I had a very sad conversation with a family

0:50:45.100,0:50:46.530
member of a patient who

0:50:46.530,0:50:49.720
was doubting that our patient had the disease,

0:50:49.720,0:50:53.200
and cited this study to say that now

0:50:53.200,0:50:56.160
there was proof that "CFS was psychological"

0:50:56.160,0:51:00.240
and that with psychological intervention, the patients "could get cured." This is far

0:51:00.240,0:51:01.109
from truth,

0:51:01.109,0:51:04.839
from the actual findings of the study. So I think we have

0:51:04.839,0:51:08.819
lots of work to do; we need

0:51:08.819,0:51:13.160
all the best minds at Stanford, and we are gathering the best minds at Stanford

0:51:13.160,0:51:16.920
around the team. We need to find an objective,

0:51:16.920,0:51:20.430
a form of saying, "yes,the patient has CFS";

0:51:20.430,0:51:23.558
we need to find black levels--

0:51:23.559,0:51:27.740
biomarkers that can identify the situation; we need to find ways to

0:51:27.740,0:51:31.580
identify the subgroup, which is the pathogen behind--

0:51:31.590,0:51:35.579
it's possible that there are patient with CFS that are not infectious as well.

0:51:35.579,0:51:39.520
We need to find those agents and to the right trials.

0:51:39.520,0:51:43.109
The attitude that was have taken at Stanford

0:51:43.109,0:51:47.529
reminds me of what we want to do, is similar to what's found in this

0:51:47.530,0:51:50.790
late 70s movie (The Wild Child) from Francois Truffaut:

0:51:50.790,0:51:54.450
they have found this child in the forest of France.

0:51:54.450,0:51:59.439
it was wild. Did not know how to speak, perhaps couldn't even hear.

0:51:59.440,0:52:03.869
Basically it was a wild child with an entity of behavior

0:52:03.869,0:52:07.329
that was not understood at all. However,

0:52:07.329,0:52:11.690
when he was brought to a room where a physician who wanted to really

0:52:11.690,0:52:14.890
help him and understand him, was trying to describe

0:52:14.890,0:52:19.890
the length of his hair, teeth, numbers of scars in his skin,

0:52:19.890,0:52:22.160
et cetera; made, uh,

0:52:22.160,0:52:25.308
(an) observation. The kid

0:52:25.309,0:52:28.420
did not react when a heavy noise

0:52:28.420,0:52:31.730
was produced in the room. And he said, "Did you notice?"

0:52:31.730,0:52:36.590
He didn't react to that loud noise. He's deaf.

0:52:36.590,0:52:40.300
Then, another man who has seen the kid in the wild,

0:52:40.300,0:52:44.200
from the village, says, "How can he be deaf

0:52:44.200,0:52:47.430
when in the large I've seen him turn around

0:52:47.430,0:52:50.770
when a nut was cracked behind him?"

0:52:50.770,0:52:55.400
So the physician who is trying to make the observation says, "Write this:

0:52:55.400,0:52:58.900
Indifferent to loud noises... whereas he turns around

0:52:58.900,0:53:02.170
when a nut is cracked behind him." So

0:53:02.170,0:53:06.339
it's really having a candid attitude towards this disease:

0:53:06.339,0:53:10.200
observing what is there, what the disease is telling us, what I think that one day,

0:53:10.200,0:53:14.790
hopefully, we'll be able to (use to) make a difference. And that would not be possible with a team.

0:53:14.790,0:53:18.819
So we're very grateful to the Brennan and Taskey families for their support;

0:53:18.819,0:53:23.359
Lindsey Merrihew, who is right here in the room--none of these things

0:53:23.359,0:53:27.140
trust me, would have been possible without Lindsey. She's really the head

0:53:27.140,0:53:31.290
and the mover and the doer in the team. And all the people

0:53:31.300,0:53:35.460
below her: Jane Norris, Amber Ruiz, Dr. Marzie Zinn, who is also here,

0:53:35.460,0:53:38.540
Dr. Marcie Zinn has given the challenge of

0:53:38.540,0:53:42.500
helping us to understand the brain fog and how to measure.

0:53:42.500,0:53:45.780
So none of those things would have happened without the intervention

0:53:45.780,0:53:51.910
of this great team. Thank you.

0:53:51.910,0:53:55.420
[Question asked] Now the doctor has asked the question that,

0:53:55.420,0:53:58.470
you know, obviously, this,

0:53:58.470,0:54:01.490
uh, we have a problem.

0:54:01.490,0:54:04.609
And it's the waiting time. Lindsey, what is

0:54:04.609,0:54:08.430
the waiting time now?

0:54:08.430,0:54:13.440
Two to three years. So we are trying to desperately try to,

0:54:13.440,0:54:16.609
um, to to cope with the high demand.

0:54:16.609,0:54:20.440
There is a physician in the area, in El Camino Hospital,

0:54:20.440,0:54:23.980
[Dr. Andreas Kogelnik]. So [K-

0:54:23.980,0:54:27.690
0-G-E-L-N-I-K.]

0:54:27.690,0:54:30.240
And Lindsey and I can give you his contact information,

0:54:30.240,0:54:33.970
who is seeing now patients with chronic fatigue syndrome, with an approach

0:54:33.970,0:54:37.649
similar to ours. So that has helped us, to

0:54:37.650,0:54:40.900
have patients being seen by him.

0:54:40.900,0:54:44.599
Thank you, yeah, you are correct, it's right here, his name:

0:54:44.599,0:54:48.230
Kogelnik, actually. K-O-G. Kogelnik.

0:54:48.230,0:54:52.190
Um, so, but... you know, our hope,

0:54:52.190,0:54:55.790
our goal, in addition to one day

0:54:55.790,0:54:59.220
be able to understand the disease and erradicate it,

0:54:59.220,0:55:02.868
in addition to that dream, is that we need to desperately bring

0:55:02.869,0:55:06.319
education our colleagues, medical students,

0:55:06.319,0:55:09.720
fellows residents, so they can perpetuate that

0:55:09.720,0:55:12.730
model. [Question asked] So the question was made that,

0:55:12.730,0:55:17.309
what was the dose that was used in the study that we cited in the late 80s,

0:55:17.309,0:55:20.849
where patients with chronic fatigue syndrome were treated with acyclovir,

0:55:20.849,0:55:23.859
and the answer is that they used the standard dose

0:55:23.859,0:55:26.930
for that time, that were not high doses.

0:55:26.930,0:55:30.710
And what is striking is they used only five weeks,

0:55:30.710,0:55:34.400
yet they went out and made that as the Bible,

0:55:34.400,0:55:38.329
that antiviral intervention does not work for CFS.

0:55:38.329,0:55:41.670
[Question asked] The question is, if valgancyclovir is available.

0:55:41.670,0:55:46.150
Yes. It is available; it's approved by the FDA;

0:55:46.150,0:55:49.470
when we did the trial, we went to the FDA,

0:55:49.470,0:55:53.589
got the permission at the FDA to use it for this other indication.

0:55:53.589,0:55:56.630
It needs medical supervision--

0:55:56.630,0:55:59.950
there is a safety issue with the blood cells, but

0:55:59.950,0:56:03.529
if you have proper supervision, that usually is not an issue.

0:56:03.530,0:56:06.990
There is a question mark on the long-term use about,

0:56:06.990,0:56:11.529
in animals, it can cause cancer, we do not know if that happens in humans, but it

0:56:11.530,0:56:12.900
has to always be

0:56:12.900,0:56:16.890
discussed with your provider in that regard.

0:56:16.890,0:56:19.339
[Question asked] So the question is, like--could people, knowing

0:56:19.339,0:56:24.569
that some of these infections can do that devastation, can you do something

0:56:24.569,0:56:28.359
in a prophylactic manner, to prevent that [you're] going to that

0:56:28.359,0:56:32.390
unhealthy cascade. Not that we know of.

0:56:32.390,0:56:37.848
If we were to write something in a magazine, in a journal, we

0:56:37.849,0:56:41.619
would have to say "nothing is known." If we were having a

0:56:41.619,0:56:45.910
coffee table conversation, then you could say some things like,

0:56:45.910,0:56:50.149
"Please don't--you know, there are many patients who, when they are sick, they try

0:56:50.150,0:56:53.900
to go to the extreme, they try to to back to work naturally.

0:56:53.900,0:56:57.740
I would suggest that common-sense measures of rest when they have the

0:56:57.740,0:56:58.759
acute illness

0:56:58.760,0:57:03.859
be exaggerated, in fact--that they take more time to rest.

0:57:03.859,0:57:07.790
The other thing that we have found, but this is totally anecdotal, is some of the

0:57:07.790,0:57:11.710
kids of our colleagues at Stanford who have come down with the acute

0:57:11.710,0:57:15.160
infections, and we have measured the [levels] and they had been positive;

0:57:15.160,0:57:18.299
we had given the antibiotic right there

0:57:18.299,0:57:21.780
and it seems like--but it's very anecdotal--that they

0:57:21.780,0:57:25.329
recover. But, anecdotal. [Question asked] The question is about

0:57:25.329,0:57:28.980
the levels of HSV-1, or HSV-2,

0:57:28.980,0:57:33.730
and even with HSV-6--do they travel travel together?

0:57:33.730,0:57:37.780
Preliminarily, it seems like the EBV and HSV-6,

0:57:37.780,0:57:42.569
they travel together in a surgroup of patients. We thought that that surgroup was gonna be

0:57:42.569,0:57:46.420
large, the one that we allegedly found,

0:57:46.420,0:57:49.549
but he seems like it's a small surgroup.

0:57:49.549,0:57:54.220
It's rare to have a patient with HSV-1 and HSV-6.

0:57:54.220,0:57:58.240
We don't know why yet. Or HSV-2 and HSV-6.

0:57:58.240,0:58:01.490
It's not not uncommon to have HSV-1 and HSV-2.

0:58:01.490,0:58:05.118
And the levels of antibodies seems to be high.

0:58:05.119,0:58:09.150
We have had a surgroup of patients with

0:58:09.150,0:58:12.260
HSV-2, genital, HSV-1,

0:58:12.260,0:58:16.890
oral blisters, and we have intervened them with acyclovir, which is a much

0:58:16.890,0:58:19.180
simpler drug to give.

0:58:19.180,0:58:22.419
And after a year, year-and-a-half intervention,

0:58:22.420,0:58:26.240
It seems that we see these recoveries that are truly dramatic.

0:58:26.240,0:58:30.618
In a surgroup of patients. Ideally we should do

0:58:30.619,0:58:34.720
a randomized trial; I'm trying to see how we can come up with the funds

0:58:34.720,0:58:38.640
to do the right study, similar to the other, to prove that that's the case.

0:58:38.640,0:58:43.500
[Questions asked] Two questions: one is, if the drugs that I show you, the one that we have used,

0:58:43.500,0:58:48.200
if they're anti-retroviral, meaning anti-HIV drugs,

0:58:48.200,0:58:52.140
what I have shown you--emphasize that--what I have shown you

0:58:52.140,0:58:55.540
they are not anti-retrovirals; they are not anti-HIV.

0:58:55.540,0:58:58.710
And the second question: if there,

0:58:58.710,0:59:01.920
if there is like a stem cell base for the disease,

0:59:01.920,0:59:06.339
because the virus can get into, some other viruses can get into the genetic

0:59:06.339,0:59:09.710
code, and the answer is, "not as far as we know."

0:59:09.710,0:59:13.420
It seems like it has to do more with the germ line cells.

0:59:13.420,0:59:16.460
The very early cells, but not stem cell

0:59:16.460,0:59:21.530
based. And as far as we know it's not stem-cell based.

0:59:21.530,0:59:24.960
But there is very litle known about that part.

0:59:24.960,0:59:29.140
[Question asked] So the question is about: if long-term,

0:59:29.140,0:59:33.290
careful, safe, thoughtful,

0:59:33.300,0:59:37.619
antiviral or anti-microbial intervention can result in the improvement of

0:59:37.619,0:59:43.890
chronic diseases like this. So that's the model that we are operating. So the--

0:59:43.890,0:59:46.890
if you see what we're doing behind, it suggests that

0:59:46.890,0:59:50.240
infection at low levels can do a lot of stuff. That's

0:59:50.240,0:59:53.259
the model that we are using. And then that's--

0:59:53.260,0:59:56.410
So pressing that for long periods of time should improve. So

0:59:56.410,1:00:00.980
the question suggests the possibility that what about if we did that,

1:00:00.990,1:00:05.640
for the long term effects of varicella-zoster virus, or shingles virus

1:00:05.640,1:00:09.879
in terms of pain, this is well known, that it can do this problem.

1:00:09.880,1:00:13.670
Preliminary--but again, just two small patients, but

1:00:13.670,1:00:18.520
highly gratifying. We have patients who had come to us for five years of

1:00:18.520,1:00:21.720
pain, that is clearly what we call the

1:00:21.720,1:00:24.910
"herpes without rash."

1:00:24.910,1:00:28.470
and this woman, after like a year and a half of acyclovir, is

1:00:28.470,1:00:29.430
back to like,

1:00:29.430,1:00:32.930
smile, bubbly personality, normal--

1:00:32.930,1:00:36.690
those are anecdotal. The point is,

1:00:36.690,1:00:41.790
I think it calls for that. It calls for patients who have the shingles

1:00:41.790,1:00:44.490
to be randomized to long term antiviral suppression

1:00:44.490,1:00:49.598
versus not to show whether it has an impact on the post-herpetic pain

1:00:49.599,1:00:52.690
or neuralgia. Very good point. [Question asked] What about

1:00:52.690,1:00:57.300
families who share the same environment, who could have the same markers. And,

1:00:57.300,1:01:01.599
the right study has not been done, though we do have,

1:01:01.599,1:01:06.910
I think it's--correct me if I'm wrong, Lindsey, but we have four families now,

1:01:06.910,1:01:11.490
four families, in whom they share the markers,

1:01:11.490,1:01:14.400
and not all of them express the disease. So it looks like

1:01:14.400,1:01:18.910
something else is needed. So we have four families who had that behavior.

1:01:18.910,1:01:23.200
So it seems that you need more than the infection to express disease.

1:01:23.200,1:01:26.500
[Question asked] The question is, are we testing patients for XMRV.

1:01:26.500,1:01:30.990
So we asked the Microbiology Department at Stanford

1:01:30.990,1:01:33.579
and they are stepping up to the plate. They are

1:01:33.579,1:01:38.109
setting up the test. We need to find a few more resources, but they are,

1:01:38.109,1:01:41.420
they are doing it. And some of our patients are doing it

1:01:41.420,1:01:44.780
through the other--it is a commercial laboratory that now,

1:01:44.780,1:01:48.170
that's it. Good question. [Question asked] The question is are there any

1:01:48.170,1:01:52.430
clinical trials? There are clinical trials of (a) different nature and kind.

1:01:52.430,1:01:55.848
There is, for example, a clinical trial with interferon.

1:01:55.849,1:01:59.650
Interferon is an antiviral, and it's given to patients with the hope that they

1:01:59.650,1:02:03.839
will recover. And that's (they are) the Nevada group.

1:02:03.839,1:02:07.490
There are others in Europe that obviously our patients will not have access to.

1:02:07.490,1:02:11.430
Our idea, our dream, is to have

1:02:11.430,1:02:14.879
a whole group at Stanford that would just do

1:02:14.880,1:02:18.440
clinical trials for these kinds of patients. But that is an

1:02:18.440,1:02:22.839
infrastructure that is relatively large. And unfortunatel, the NIH

1:02:22.839,1:02:26.420
does not give much money for clinical trials, and that's

1:02:26.420,1:02:30.900
unfortunate. [Question asked] So the question is about the role of alternative treatments.

1:02:30.900,1:02:35.180
What (I've) shown you, the role of cognitive-behavioral intervention,

1:02:35.180,1:02:39.520
the, sort of like, physical therapy intervention,

1:02:39.520,1:02:42.799
clearly points to the fact that there are

1:02:42.799,1:02:46.920
things that patients can do that could be thoughtful,

1:02:46.920,1:02:50.619
not expensive, that could work for the patient.

1:02:50.619,1:02:53.900
So there are things that the patients can do, and they can

1:02:53.900,1:02:57.240
be helped. The answer is yes. And they are in the alternative

1:02:57.240,1:03:02.288
[Question asked] The relationship--is there any any relationship between fatigue,

1:03:02.289,1:03:05.559
that is temporal, versus chronic fatigue,

1:03:05.559,1:03:08.579
because as it's pointed (out), some interventions

1:03:08.579,1:03:11.630
from a good cup of coffee, or provigil,

1:03:11.630,1:03:14.960
or ritaline, make patients with short-term fatigue

1:03:14.960,1:03:18.950
better. There is a subset of patients with chronic fatigue

1:03:18.950,1:03:22.299
syndrome that experience that temporal improvement with those same

1:03:22.299,1:03:23.369
interventions,

1:03:23.369,1:03:27.390
but they are not lasting. All of them tell us,

1:03:27.390,1:03:30.680
when they use those interventions, they basically lead them to

1:03:30.680,1:03:33.788
overdo it and crash. And it's very

1:03:33.789,1:03:38.000
short-term--the effect is very short-term.

1:03:38.000,1:03:42.300
We don't know if the same thing that causes fatigue

1:03:42.300,1:03:46.100
are the same mechanisms that cause chronic fatigue. Our suspicion is that there are

1:03:46.100,1:03:50.510
two different things doing it. Because the patient who had the chronic fatigue,

1:03:50.510,1:03:53.530
more than the fatigue, they have all these other other symptoms.

1:03:53.530,1:03:56.910
Many of them describe--it's like having a bad flu

1:03:56.910,1:04:00.618
going on for years, or for decades. [Question asked] So the question is, are we

1:04:00.619,1:04:04.200
seeing family members of patients with chronic fatigue syndrome

1:04:04.200,1:04:07.859
higher incidents of autoimmune problems?

1:04:07.859,1:04:10.980
The answer is yes. It seems like they tell us stories

1:04:10.980,1:04:14.900
about patients having a higher--the patients tend to have more

1:04:14.900,1:04:18.410
thyroid problem(s) of the autoimmune type. Um,

1:04:18.410,1:04:22.288
we are starting to pay attention to vitiligo, which is

1:04:22.289,1:04:26.200
whitening of the skin when the melanocytes are attacked by

1:04:26.200,1:04:29.680
antibodies. So it seems like there is another

1:04:29.680,1:04:33.348
clue towardas autoimmunity there.

1:04:33.349,1:04:36.480
[Question asked] Are the HSV-6 titers easily done and the answer is

1:04:36.480,1:04:40.380
yes. We don't have any commercial tie with

1:04:40.380,1:04:44.000
anybody. But there is a lot that we suggest

1:04:44.000,1:04:47.130
where the HSV-6 titers can be done, and its

1:04:47.130,1:04:50.609
focus, only because we are familiar with their numbers,

1:04:50.609,1:04:55.470
we have learned to to know what is low, what is medium, what is high.

1:04:55.470,1:04:59.240
But we have no commercial connection with them, but focus laboratory

1:04:59.240,1:05:02.720
appears to be reliable in giving us titers that we can

1:05:02.720,1:05:07.189
sort of like, act upon. [Question] So it's been said that there are,

1:05:07.190,1:05:11.299
there is a support group based in Mountain View,

1:05:11.299,1:05:14.390
that there is a sign up sheet outside here,

1:05:14.390,1:05:17.450
and it's important to share

1:05:17.450,1:05:20.618
these experiences. It's important to

1:05:20.619,1:05:25.180
bring this together, and as it was shown in that study in The Lancet,

1:05:25.180,1:05:29.379
it sounds like having interventional, behavioral intervention,

1:05:29.380,1:05:31.160
cognitive intervention,

1:05:31.160,1:05:34.279
it seems like it helps. And it's very important that,

1:05:34.280,1:05:38.859
that--do not let people talking to--that study proves

1:05:38.859,1:05:42.130
that CFS can be cured, or that that study proves

1:05:42.130,1:05:45.849
that it's psychological. In addition to what you said, they excluded patients

1:05:45.849,1:05:50.289
who couldn't come to the hospital, so the sickest patients didn't make it into the trial.

1:05:50.289,1:05:53.930
Though their scores were really low in terms of performance,

1:05:53.930,1:05:57.609
so in addition to the selection issues,

1:05:57.609,1:06:01.470
the study does not prove a psychological (connection) and does not prove

1:06:01.470,1:06:04.629
that that's the way to cure patients. [Question asked] Is there any

1:06:04.630,1:06:08.240
there any neurological or phenotyping difference, phenotype difference, between

1:06:08.240,1:06:10.709
those patients who come down with an

1:06:10.710,1:06:14.380
illness, with CFS, after they have an acute illness,

1:06:14.380,1:06:18.369
particularly an infectious illness, versus those who have their onset

1:06:18.369,1:06:22.619
not associated with an infection? Not that we know of,

1:06:22.619,1:06:26.390
but we are separating them by when we take the history,

1:06:26.390,1:06:29.670
and in the analysis that we are doing, looking for pathogens, or for immune

1:06:29.670,1:06:31.230
response abnormalities--

1:06:31.230,1:06:34.920
we are taking that into account. So hopefully we'll be able

1:06:34.920,1:06:39.880
to answer--no, I think he's asking like, independent of (whether) it's a woman or man,

1:06:39.880,1:06:43.750
is there a difference between those who started the illness with an infection,

1:06:43.750,1:06:47.700
versus those do do not start the disease with an infection.

1:06:47.700,1:06:51.180
It is well-known that 75 percent of the patients with

1:06:51.180,1:06:55.780
CFS, 75 percent are women. Now

1:06:55.790,1:06:59.520
if we were to take women alone, there are women who started their CFS

1:06:59.520,1:07:04.849
without an infection. And so the sample size on the second study was very small.

1:07:04.849,1:07:08.119
But women can start their CFS with not an infectious illness.

1:07:08.119,1:07:11.460
And the question is, are there differences between those who,

1:07:11.460,1:07:14.670
who tell you the precise time where they started,

1:07:14.670,1:07:18.900
versus those who who did not. So the question is, when the patients get a

1:07:18.900,1:07:20.100
viral illness,

1:07:20.100,1:07:23.339
some of them go into CFS and some do not.

1:07:23.339,1:07:28.200
The most common factor that has been associated in the study

1:07:28.200,1:07:31.400
(that) have looked at this, is severity of the illness.

1:07:31.400,1:07:34.799
So the more severe the illness, the more likely they are

1:07:34.799,1:07:37.940
to go into having the illness--

1:07:37.940,1:07:42.130
as far as it's known. [Question asked] Well thanks to the support of one of our

1:07:42.130,1:07:45.480
patients, we started, Lindsey actually,

1:07:45.480,1:07:48.920
and Mrs. Kaski are really the people who

1:07:48.920,1:07:52.490
we have to thank. We started a website

1:07:52.490,1:07:56.599
where, at Stanford, and, Lindsey, the name of the website please?

1:07:56.599,1:07:59.720
so http://chronicfatigue.stanford.edu/

1:07:59.720,1:08:03.578
...and there we are starting to put up as many resources as

1:08:03.579,1:08:06.950
we can, everything that we have learned about,

1:08:06.950,1:08:10.868
of the disease for the past few years. [Question asked] We know that some patients

1:08:10.869,1:08:14.630
crash. Have we measured the amount of dividers

1:08:14.630,1:08:17.899
or cytokines during those crash periods?

1:08:17.899,1:08:22.540
so we attempted to do that in the study that I showed you, where we found differences.

1:08:22.540,1:08:26.350
But the numbers are so small, and we didn't see any differences.

1:08:26.350,1:08:29.969
But I think it's a matter of just doing that.

1:08:29.969,1:08:34.799
The tough part of studying that is, how can you justify

1:08:34.799,1:08:39.890
to ask a patient, "Take this drug. It's gonna make you sick,

1:08:39.890,1:08:42.620
and we'll study you." So ethically it's hard. [Question asked]

1:08:42.620,1:08:46.799
These viruses are latent. They are there for the life of the patient.

1:08:46.799,1:08:50.299
So we are not suggesting that with these long-term anti-

1:08:50.299,1:08:53.509
viral interventions we are eradicating the

1:08:53.509,1:08:57.549
virus out of the body, we are trying to, if our theory is correct,

1:08:57.549,1:09:01.819
bring them under control. So--and you are absolutely correct--

1:09:01.819,1:09:04.969
I think that part of the reason it has eluded

1:09:04.969,1:09:09.799
our understanding of the disease, is that they are at very low levels

1:09:09.799,1:09:12.939
even when they are causing disease. That is correct.

1:09:12.939,1:09:16.108
[Question asked] It's more common in women--have we seen mothers

1:09:16.109,1:09:20.120
giving it to their daughters? So we have,

1:09:20.120,1:09:24.599
sadly, a few cases where that has been the case.

1:09:24.600,1:09:28.238
And mostly related to that situation, where dividers

1:09:28.238,1:09:32.448
integrate into the chromosome, the human herpes--so herpes viruses

1:09:32.448,1:09:35.689
normally do not integrate into the chromosome

1:09:35.689,1:09:39.669
like HIV does, like the XMRV does,

1:09:39.670,1:09:44.120
herpes viruses are known for not doing that. But the HSV-6 has found a

1:09:44.120,1:09:48.839
clever way to do it, and they--those patients

1:09:48.839,1:09:53.420
seem to pass their virus, particularly mothers to daughters,

1:09:53.420,1:09:56.929
through their chromosomes. So there are situations,

1:09:56.929,1:10:00.300
but that's the exception, luckily. But it's--

1:10:00.300,1:10:04.500
these are the tougher (cases) to deal with. [Question asked] So the question is very clever. So the same

1:10:04.500,1:10:05.929
way we can prevent--

1:10:05.929,1:10:11.909
and that is true--we can prevent HIV-infected mothers from giving HIV to their babies.

1:10:11.909,1:10:15.759
Can something like that be done for mothers with CFS?

1:10:15.760,1:10:19.800
Unfortunately, the drugs

1:10:19.800,1:10:22.540
can damage the baby, theratogenic, so that

1:10:22.540,1:10:25.890
makes it very hard to justify doing it with our

1:10:25.890,1:10:30.650
proper study setting. So that makes it very hard. But

1:10:30.650,1:10:33.670
I was at a meeting last night in

1:10:33.670,1:10:36.710
in Washington, with a patient who has

1:10:36.710,1:10:40.730
her daughter with it, and she once--her daughter,

1:10:40.730,1:10:44.919
through the treatment that we did, went back to complete normality after years of

1:10:44.920,1:10:48.940
having the illness. And they are now desperate that she got married,

1:10:48.940,1:10:52.990
newly married, and they want to have a baby, et cetera. How do you do it?

1:10:52.100,1:10:55.550
At this point there is nothing we can do. Unfortunately.

1:10:55.550,1:10:59.140
[Question asked] Two points: one is, do we have ways to

1:10:59.140,1:11:03.469
standardize what we are doing, so other physicians can have easy access

1:11:03.469,1:11:08.380
to doing those steps, and following the--the answer is yes.

1:11:08.380,1:11:11.659
And we talk to other physicians who are--

1:11:11.659,1:11:15.230
So many physicians had doing this now, nationwide,

1:11:15.230,1:11:19.590
and sometimes the patients, after they have been on the waiting list, they come to us

1:11:19.600,1:11:22.190
after they have been treated. And we're just fine-tuning the issues.

1:11:22.190,1:11:25.860
so we do have standard formats

1:11:25.860,1:11:29.159
that we give out to physicians.

1:11:29.159,1:11:32.509
And I think that I can say that, because

1:11:32.510,1:11:37.190
it's legal, and medically viable, we can actually put those protocols in

1:11:37.190,1:11:38.629
the website as well,

1:11:38.630,1:11:42.110
because none of the drugs that we personally,

1:11:42.110,1:11:45.710
we at the clinic are using, none of them are experimental.

1:11:45.710,1:11:49.699
They are all FDA-approved. And as you know,

1:11:49.699,1:11:54.849
any physician has the freedom to use any drug that is approved by the FDA for any

1:11:54.850,1:11:56.890
other indication that is reasonable.

1:11:56.890,1:12:01.179
so that is not illegal. And we put those protocols

1:12:01.179,1:12:04.280
in the website so physicians can download them.

1:12:04.280,1:12:07.730
But in the meantime, they can call us, and we give them out, and we talk to the

1:12:07.730,1:12:11.610
physicians as well. Regarding the equilibrium--

1:12:11.610,1:12:14.809
That is a drug

1:12:14.810,1:12:18.110
that comes from China, so we don't prescribe it because we we cannot

1:12:18.110,1:12:23.259
guarantee what--how many milligrams and the purity of the drug,

1:12:23.260,1:12:27.320
but if the suspicion is that other kinds of viruses called

1:12:27.320,1:12:31.920
entero- or echoviruses are behind it, we highly suggest the patient to

1:12:31.920,1:12:35.280
consult Dr. Chia in Southern California, because he

1:12:35.280,1:12:39.120
really is the one with the expertise, and that's his baby,

1:12:39.120,1:12:42.519
and I totally trust that what he has found is valid.

1:12:42.520,1:12:46.489
But we don't have the expertise with the administration of the drug.

1:12:46.489,1:12:47.500
Thank you. [Applause]