Dr. Mikovits transcription
If anyone sees an error in my interpretation of what I thought I heard, or some incorrect terminology, I'd appreciate it if you would let me know. Thanks in advance
Dr. Judy Mikovits, January 22, 2010, Video 2 Section 8, 30 mins-45 mins
(Q & A)
Question: Inaudible
Dr. Judy: We have looked in a limited number of families that we’ve done, and in fact, maybe only one member of the family has CFS, and so it will be an interesting year, but, um, once these families and the various diseases and trying to understand – it’s a very slow replicating virus so it really just sits there for a long time.
So if you can keep the reservoirs low, you might have the virus your whole life and never get sick. We don’t know how long it’s been in the population. We think like with other retroviruses, the younger you get sick, the more severe the disease.
If you give it to the rats when they’re neonates, they get cancers. If you get it at 30 or 40, they don’t get anything.
So the immune system is educated and grows as you go along. It may be more fragile at different times in your life. We’ve seen a lot of it at puberty, boys and girls alike. There’s a lot of infection or at least apparent infection, disease occurrences at 12 or 13. And I do know that’s when Andrea got sick. (to Annette Whittemore) And presumably, your family was in the same space, but there was no other disease or child you had at puberty at that point.
Retroviruses don’t infect people differently. You can’t go to Germany and say the reason they don’t have it is because they have hardier genes in Germany, because everybody gets infected. It’s just which immune system can control the virus and keep it down.
Since we’ve been able to treat HIV/AIDS now, we find there are elite controllers. People are walking around with HIV who never knew they had HIV, and the copy numbers are all low. Their immune system is fine, and they have no idea when they got infected.
Question: So a lot of patients say they had a flu, a weird flu, a week or two before they got CFS. So what you’re saying is that flu-like illness is a bug that came along and allowed the XMRV to create CFS?
Judy: Well, no. What I think is happening is – I know almost nothing about CFS – but what we think is happening is – remember the slide where I showed you those little events? You know, what was the event that was the straw that broke the camel’s back?
Where did the balance tip between, where you’ve got your immune system working well and the virus and the immune system are co-existing just fine, then some other, that other bug, whether it be lime, a flu, a anything, GETS YOU.
And the virus, the cells divide, and cause the B and T cells you need to mount an immune response. And now you’ve got your memory population that might have been harboring the virus and it’s replicating ‘cause it’s seen that same pathogen before, so it could be a common everyday pathogen, and then you just tip the scale to where now your immune system can’t handle it or any. And every day you’re seeing more and more infection ‘cause you’re NK cells aren’t working, your B cells aren’t working.
We put that antibody up there for a reason, we haven’t been able to correlate the levels yet, because we haven’t been able to find high enough numbers, but we do see these infected families where infected spouses and things have very high levels of antibodies, that suggest maybe these antibodies in the retrovirus can be protective, and maybe there’s an immune therapy on the horizon as well.
So you can think about it in that way. It doesn’t have to be the insult. You might not know how long you harbored that virus, or it could be….
Question: So what you’re saying is XMRV was there, then something else came along that was the tipping point.
Judy: Yes, that was the tipping point, that’s correct. That’s our hypothesis. And again, it’s testable, we don’t know.
Question: (partially inaudible) Is there differences between – ‘cause you’ve got a big population with sudden onset and then you’ve got a big population that had a gradual onset. And a lot of the gradual onset patients are worried that they don’t fit this equation. So what would you say to that?
Judy: That the bump is smaller, it’s not a huge burst. So little insults over time. I think, for me anyway, I know it’s only a handful that I’ve looked at, that I know the patients and I know what the onset was. So sudden onset, gradual onset – it just depends on what the environment was, the triggers and what the events were that spurred it on. So I don’t see that if you were gradual onset, that you might not be infected as well.
Question: That’s an important thing to know.
Question: Have you tracked any of the inflammatory markers in the blood with the XMRV virus?
Judy: Yes.
Question: What are you finding?
Judy: We find a signature suggesting a viral infection, an unclear viral infection. So we have 5-10 inflammatory cytokines and chemokines that will cluster in an infected person. But the problem is, that we don’t know if it indicates active infection. Certainly when the virus is quiet those cytokines will go down and those cytokines will change, and it might be a nice biomarker for following active infection, but we haven’t analyzed the data in that way yet. So it could very well sit, and some of those go down and up very quickly. So like 3 days you’re up at IL-6 or IL-8, then some of the chemokines are elevated and then they go back , like an EEG. Just like you might assume the retrovirus could be an EEG, depending where in the body that is is. We don’t know the reservoirs, so we don’t know what’s controlling it.
Question: I’m confused about something. You say you can’t find it very easily by PCR, so you are culturing it. Then how did you find it for the Science paper?
Judy: Well, because I found it in 67%, by PCR, of the patients, but I looked several times, at any given time. I just said it's like an EEG. So I got lucky and found it when the patient was high. They’ll come to the doctor when they’re sick which might mean they’re replicating more WBCs and there’s more virus in their WBCs.
Question: So you checked these patients multiple times over time?
Judy: No, I did them all at the same time because they were in the repository. So we collected those samples multiple times over time.
Question: So you took like 10 samples from one patient?
Judy: No, usually it was four. A Poisson distribution, the copy number could be as low as 5 or 10 copies per mil of blood, so there’s a statistic called Poisson distribution, you might find it one out of three times so we went more than one and in most people we found it.
Question: So the UK paper had studied patients. If they would have looked at 4 or 5 per patient, do you think they might have found it?
Judy: They might have certainly found more, yeah.
Question: They essentially accused you of contamination.
Judy: Right. But why would I have contaminant in my sick people and not my healthy people? How would I do that? I did it in three different labs. I did it in Cleveland Clinic. When I first came to the Institute, we didn’t have a lab, so everything we drew from around the world, I sent to Frank’s office. They processed it. I went there, I put it in the microarray or whatever I was going to do, and we worked there for a couple of weeks, you know, while we were building our lab and finally got started.
So there, from the way we did the study there’s just NO possible way there was contamination. And that’s what the reviewer concluded. And the phylogenetic analysis proved two things. It wasn’t a mouse virus, it’s a human virus; it wasn’t a contaminant from a lab. We never do mouse work anyway, but it wasn’t a contaminant from mouse feces or something in the lab and it was clearly a new branch of the (phylogenetic) tree. A human virus. And our virus wasn’t exactly the same as the prostate virus. It’s still XMRV, because it’s 99% the similar. But that’s enough to show it wasn’t a contaminant.
One of the things you have to use to get a good PCR is at least 750 nanograms of DNA. They have no idea how much DNA was there. And they quantified 3-9 out of 186. Sure they found a band of globins, but globins are in every single cell, so again, you’re making an unfair comparison of what you’re saying you see. And then you amplify it for less cycles than what would really push the envelope.
Also to show no mouse contamination with the CDC, and Bill Switzer - after he saw the results in the paper. He said, “I have an assay that’ll show it’s a mouse virus contaminant. It’s a very sensitive, very specific PCR. Will you do it?” I said, “Sure, send it to me”. And we did it on all 100 and not a one. Not one cell line in our lab. He’s found a couple in his lab, but we didn’t find any. Perfectly controlled. He said, “Congratulations, it’s not a mouse contaminant.”
So there’s little else we can do except wait for the rest of the community. It’s there.
And the prostate people say, “oh you didn’t find it in 500 people, it must not have anything to do with prostate cancer. It just didn’t have anything to do with that population.”
And again, Norbert Bannert, is a high quality scientist and as soon as he saw the paper he called me and asked for the reagent. Because he’s gonna go back and look to see if it really is there, and help us find some answers. He’s also looking to see a CFS group. So it just depends on what you really want to find. We weren’t biased in our study. You know, I’m a cancer cell biologist and we aren’t biased.
I had to work really hard to get most of the people – not Frank and company. The NCI didn't know what CFS was. You know, fortunately, our scientists can at some level do what they want as long as it’s along with the mission. I remember one gentleman, high level NCI official, said “tell ‘em to get over it”. You know if you can’t, and again that’s a credit to Annette and the formation of the WPI. Um, we got a grant where we literally named XMRV within my first six months in 2007, because of the juxtaposition of seeing that paper in prostate cancer, right when we met.
And thinking about the possible mechanisms and the grant got rejected three times, you know, because scientifically, retroviruses aren’t in CFS. If you would have looked in Wikipedia in August, it would say retroviruses aren’t in CFS. It doesn’t say that anymore. So we made progress.
So will there be a variant? Maybe England will be a variant. Maybe there’s XMRV2, and one causes more. Maybe we found the one that causes the least severe disease, so maybe there’s XMRV2.
A group emailed me from China, and the guy said “please”, you know in very broken English, “please don’t leave me, please write me back. Please help me”. And so Sam Chow was going over there, and I said will you look up this group? And Sam Chow has found a virus that looks similar. Might not necessarily be the same virus, might be a lot more aggressive virus over there. Now that’s just anecdotal.
Question: Inaudible (something about SARS?).
Judy: I don’t know, I’m not familiar with that literature.
So we don’t know. The good news is we have something to work with that is a very testable hypothesis. This has been very rigorous. You don’t get more rigorous than Science and Frank and Sandy Ruscetti. They’re highly regarded. That entire team are experts. So the CFS population had the opportunity to have them look at us and they didn’t show any bias. They looked. You know, I asked Frank to come out to Reno before I took the job, because I said, you know, I hear a lot of things about this. So he came out and stayed a few days and saw some patients and spent some time with them. And I was on an East coast trip working. And I came back a few days later and I said, “Well, what do I do?” And he said, “Take the damn job!”.
So if you’re really looking unbiased and you look at this, it COULD be only 10,000,000 in America, it could be only endemic right here, it could be like Japan. And HTLV is fairly innocuous – only 20% get that tropical spastic paresis.