Chapter Sixteen
It was Monday morning, court had reconvened, and this was the first time Sarah had seen a witness testify by video conference link. The large overhead screen is pulled down in front of the jury, and a computer is projecting the image of a man, probably in his mid-sixties, grey hair, with a serious look on his face.
“Please spell your name for the record.” Campbell is standing at the lectern with a video camera in front of him so the witness could see him as well. Another video camera is strategically placed for a wider shot of the judge, the lawyers’ lectern, and the jury box. A video technician is available to switch the camera feed when appropriate.
“V-a-l-e-n-t-i-n-e... T-a-n-n-e-r.”
“Dr. Tanner, you’re a medical doctor?”
“I am. I graduated in Medicine from the University of Sydney, Australia in 1969.”
“And you have been awarded several distinctions?”
“Yes, I was awarded the Fellowship of the Royal Australasian College of Surgeons in 1977, and I was made a Foundation Fellow of the Australasian College for Emergency Medicine in 1983.”
“And you have a number of scientific papers you have written that have been published?”
“Correct. I have been published in the Medical Journal of Australia, Nature magazine, and the New England Journal of Medicine, and I co-authored approximately twenty other papers published in such magazines as the International Journal of STDs and AIDS, the British Medical Journal, the Journal of Infectious Diseases, and Bio/Technology.”
“And you currently reside in?...”
“Western Australia.”
“Thank you, Dr. Tanner, for being available to testify today. I realize that it’s late at night where you are.”
“About ten o’clock, yes.”
“So, Dr. Tanner, let me get right to the point.” Campbell glances at his yellow pad to verify the first question he wants to ask this witness. “Is the HIV ELISA test used in Australia?”
“Yes, it is.”
“We had a lot of testimony in the last couple of weeks about the problems associated with the HIV ELISA test. Have you had the same problems in Australia?”
“Well, I don’t know exactly what problems you’ve been told about, but I can say that the HIV ELISA test is extremely unreliable because of the high number of false positive cross reactions, and the fact that the test has never been validated using a gold standard.”
“That’s what other witnesses have said as well. And you use the same HIV ELISA tests in Australia that we use in the United States?”
“Yes, the exact same ones.”
“And to your knowledge, how long have these problems existed with the ELISA tests?”
“From the very beginning, in 1985. Have you been told that the purpose of the ELISA test was to screen blood donors to guard the blood supply from HIV contamination?”
“Yes, we heard that.”
When Tanner started, his voice was soft and hard to understand. Campbell had wondered whether it was because of the video link. But now Tanner is beginning to sound strong and clear, and the Australian accent is no longer a problem either. Maybe Tanner just had to warm up to the process. Whatever happened, Campbell is pleased with the result.
Tanner had come prepared, and he takes a quick look at some notes before continuing. “In the two years from 1985 to 1987, 30,000 blood donors a year were coming up HIV-Positive on the ELISA test, just in the United States, but everyone knew that number had to include a very large percentage of false positives from healthy donors. Finally, in 1987, the Centers for Disease Control announced that all positive ELISA test results must be confirmed by doing another test on the person’s blood, called a Western Blot, sometimes referred to as an Immunoblot; and at last, after some had waited as long as two years, 50,000 people were told they were really not HIV-Positive after all! Imagine what they went through, thinking they might be Positive all that time. And think of the hundreds of thousands of other people – their families, their sexual partners, their friends – who went through hell with them. It was truly criminal what we did to these people.”
Campbell wants to try to keep Tanner’s emotions out of the testimony. “And the Western Blot was supposed to solve this problem?”
“Let’s be very clear, because this is an important point. The Western Blot was originally designed and intended to find all the false positive reactions created by the ELISA, not to confirm the positive ones.”
It’s a good point, and I’ll come back to it later. “Dr. Tanner, please tell us what a Western Blot is.”
“Like the ELISA test, it is a test to detect antibodies to HIV in a person’s blood.”
“And how does the HIV Western Blot work?”
“Very simply, you take proteins from what is supposed to be the Human Immunodeficiency Virus, combine them with a person’s blood, and if the test changes color, you are said to be positive for that protein’s antibody.”
“That sounds just like the ELISA test. So what’s the difference between the HIV ELISA test and the HIV Western Blot?”
“First of all, in the ELISA, all the proteins from the so-called HIV are mixed together, kind of like a big soup. When the test is positive, you don’t know exactly what protein or proteins reacted. In the Western Blot, the proteins are separated into different strips, or bands – one for each protein – so you can see exactly which protein or proteins reacted to the person’s blood. Secondly, the ‘change of color’ I mentioned is different than an ELISA, in that it’s not really the color change that’s important, but the formation of blots on the bands that signify a reaction.”
“Why would that be useful – to see which proteins reacted and which didn’t?”
“When the ELISA test was getting so many false positive results, the theory was that if you could separate the proteins and see which were reacting, you could pinpoint better which proteins indicated HIV antibodies and ignore the others.”
“Did it work?”
“It might have. If certain protein bands or certain combinations of bands started showing up positive on a very consistent basis, and if those could be shown to be present in a vast majority of people with AIDS – and not present in those without AIDS – then they may have been onto something.”
Campbell understands this well, but he thinks it may have gone over the jury’s head. “Forgive me, Dr. Tanner, but I don’t understand. It sounds like you’re saying that only certain protein bands are going to react on a Western Blot.”
“Yes, correct.”
“Well, if the proteins used in the test are supposed to come directly from cultured HIV – in other words, if Dr. Gallo was claiming that the mixture he was providing was specific and unique for HIV – why don’t all of the protein bands react all the time if someone has the antibodies to HIV?”
“That would make sense, wouldn’t it? But there was already a general agreement and understanding, because of so many false positives on the ELISA test, that at least some of these proteins were not specific and unique to HIV and were causing the cross-reactions on the tests. The theory was to find out which of the proteins would only react to HIV antibodies by separating them out.”
“But that’s not what happened?”
“Unfortunately, no.”
“Why not?”
“Because there are as many problems with the HIV Western Blot test as there were with the ELISA test – and more, actually.”
Okay, here we go. Campbell is satisfied with the way his prior witnesses had destroyed the credibility of the ELISA. Now it’s time to do the same thing to the Western Blot. “What kind of problems?”
“First, the HIV Western Blot is a test that supposedly detects antibodies to HIV, like the ELISA. So testing Positive on a Western Blot means the exact same thing – that the person is HIV-Antibody-Positive, and having the antibodies to a virus like HIV should mean immunity from any disease it could cause. But since HIV has never been properly isolated, there is also no
proof that any of the proteins in the ELISA test are specific and unique to HIV; and since the Western Blot uses the exact same proteins as the ELISA, there’s no proof that any of them is specific or unique to HIV either.”
This was an important point that Campbell feels may have been lost. “Did you say the Western Blot uses the exact same proteins that are used in the ELISA?”
“Correct. Both tests are based on the so-called HIV culture that Dr. Robert Gallo patented, so they start with the same component. The only difference, as I said, was that the proteins from this culture are separated into different bands for the Western Blot.”
Campbell picks up a folded piece of paper from his table. “Dr. Tanner, this is a printed insert that comes with the Western Blot test kit manufactured by Cambridge Biotech. It says, ‘Slight ambiguities exist in the designation of the molecular weights of the HIV-I antigens. The designations listed in Figure 1 have been established by both internal testing with known markers and consensus of published literature. Could you translate that into English for us?”
“Cambridge is admitting that there is disagreement about exactly which proteins – they’re also known as ‘antigens’ – belong to HIV and should be used in a Western Blot test; and rather than using virus isolation to know what proteins to use, they chose their proteins based on their own internal tests and by taking the consensus of other people’s published studies.”
“So that would explain why you can find slightly different proteins being used in the various Western Blot test kits from different manufacturers?”
“Correct. As I said, since HIV has never been properly isolated, no one knows for sure exactly what proteins to use. So Cambridge, and all the rest of the Western Blot test kit manufacturers, have to put this disclaimer in their box to protect themselves legally.”
Campbell takes his time before asking the next question. Tanner uses the opportunity to take a drink of water while everyone watches on the video screen. Finally, Campbell asks, “You said there were other things wrong with the Western Blot?”
“Yes. Like the ELISA test, the Western Blot has never been validated, meaning that its results have never been confirmed by finding actual HIV in people who test Western Blot Positive. So there is no gold standard, as we call it.”
“We heard about the gold standard last week, Dr. Tanner.”
“Fine. What this means is that the HIV Western Blot is susceptible to the exact same false positives that the ELISA is, in terms of cross reactions of the various proteins.”
“But I thought the Western Blot was supposed to eliminate these false positives?”
“Again, that was the theory. But the theory doesn’t work in practice in this case, because the proteins used on both the ELISA and Western Blot are the same and have been proven to cross-react with antibodies to other diseases and conditions. In fact, no one is supposed to take a Western Blot test without having at least two prior positive ELISA tests, because the Western Blot produces too many false positives by itself. According to one study in 1993, there was as much as a forty-percent chance of having a false result on a Western Blot by itself.”
“So if someone takes a Western Blot as their first HIV test….”
“…they are about as likely to get a false positive result as if they took an ELISA test.”
“Is that why the Western Blot is not used in some countries of the world?”
“Yes.”
“Objection. The witness has no personal knowledge of what decision-making process was used in other countries.” At long last, Armand is visibly upset with this testimony. Sarah wonders why, after all that’s come before it, this particular line of questions would get to him. Maybe it’s simply the sheer volume of damning information that Armand didn’t expect.
The judge was surprised at the tone of Armand’s voice as well, but he had a point. “Sustained.”
“I’ll rephrase, Your Honor.” Campbell wasn’t about to let this point go. “Dr. Tanner, is the Western Blot used in Great Britain, for example?”
“No, it’s not.”
“And what is your personal opinion, rather than your expert testimony, of why not?”
“Because the Western Blot, on its own, produces so many false positives that it makes no sense to use it in conjunction with any other test, like an ELISA, that also produces an enormous number of false positives.”
Campbell waits for Armand to object, but he didn’t. Maybe Armand realizes that he needs to cool down. Well, let’s keep going and see what happens. “Dr. Tanner, are those the only things wrong with the HIV Western Blot test?”
“No, not by a long shot. The biggest problem is that, unlike the ELISA test, the Western Blot requires subjective interpretation of its results, making it impossible to standardize. Any other diagnostic test is only considered valid if the results have the same meaning in all patients, in all laboratories, by all doctors, and in all countries. That’s not the case with the HIV Western Blot.”
“Can you give us an example of what you mean by ‘standardization’?”
“Well, I think everyone is familiar with what is called an EKG – a computer printout of the rhythms of the heart. Can you imagine the chaos that would be created if the same EKG could be interpreted to mean a heart attack by one doctor in one place, but not by another doctor in another place?”
Campbell lets that one sink in while he pretends to look at his notes. “But you’re suggesting that the Western Blot, which is supposed to clear up all the confusion created by the unreliable ELISA tests, doesn’t provide that standardization?”
“It actually makes it worse, Mr. Campbell.”
“Please tell us how.”
“Mainly because no one can agree on which proteins need to react, and in which combinations, to definitely say that the test is now specific for HIV and nothing else.”
“And how did that happen?”
Tanner’s on a roll, and he knows it. This is where his expertise is matched by no one else in the world. “Initially, the two men who supposedly co-discovered HIV – Dr. Robert Gallo of the U.S. National Institutes of Health, and Dr. Luc Montagnier of the Pasteur Institute in France – couldn’t even agree. Montagnier said that just having the p24 protein was sufficient to define a positive Western Blot, even though p24 was not found in all AIDS patients. Gallo, on the other hand, said that just gp41 was sufficient, even though Montagnier himself had said that gp 41 may be due to contamination of the virus by cellular actin. Actin is an extremely common protein that is present in all cells, not just HIV, by the way. So the Centers for Disease Control compromised and said that either p24 or gp41 was enough for a positive test result; but they were getting far too many so-called ‘confirmed’ Positives for that to be right.”
“Too many? I don’t understand.”
“The number of ‘confirmed positives’ was still way too high using just p24 and gp41, and included a large group of blood donors the CDC knew couldn’t be HIV-Positive.”
Tanner coughs, and then takes another drink of water before continuing. “Excuse me. Where was I? Oh, yes. So in 1987, when the FDA licensed a Western Blot test kit manufactured by the DuPont Company, they required one protein from each of the three different HIV genes to constitute a Positive test result.” Tanner suddenly stops. “Maybe I’ve gone into things you haven’t heard about yet. Have you had testimony about the HIV genes?”
Campbell is pleased that Tanner is being so careful not to go too fast. “No, we haven’t, so please explain briefly.”
“HIV is supposed to contain three genes, and these three genes create the proteins that we’ve been talking about. There’s a gag gene, which determines the structural elements of the virus; a pol gene, which is common to all retroviruses like HIV and is involved in reverse transcriptase; and an env gene, which produces the proteins found on the membrane, or envelope, of the virus. These env proteins are called glycoproteins (gp) because they extend out from the membrane of the cell and are combined with a carb
ohydrate.”
Campbell is suddenly concerned about putting the jury to sleep. However, he has no choice. This information is critical to understanding the next part of Tanner’s testimony, and he simply has to take the chance.
“Can you wait a minute, Dr. Tanner?” Campbell moves the large easel in front of the vacant witness stand so that the wide-angle video camera can see it, along with the judge and jury. He then asks the video technician to change to that camera so that Tanner could see the easel as well. He flips to the list of the ten proteins Dr. Richardson had discussed:
gp160
gp120
gp41
p66/68
p51/53
p31/32
p55
p40
p24
p17/18
“Dr. Tanner, we’ve had testimony about these ten proteins. These are what you’re talking about, I presume?”
“Yes. But you should add that the top three proteins are the env proteins…”
Campbell draws a red line under gp41 and writes ‘env’ on top of the first three.
“…and the next three are the pol proteins…”
Another red line under p31/32 and ‘pol’ on top of that group.
“…and the bottom four are the gag proteins.”
After Campbell writes ‘gag,’ the chart looks like this:
ENV
gp160
gp120
gp41
__________
POL
p66/68
p51/53
p31/32
__________
GAG
p55
p40
p24
p17/18
Campbell asks, “Dr. Tanner, shall I keep the camera on this list while we continue?”
“Please.”
“Alright. Then please explain the relevance of these three types of proteins.”
“Well, as I was saying, the HIV Western Blot test kit that duPont created requires three proteins to light up – that’s what we call it when a protein band reacts, ‘light up’ – for the test to be called positive. They were: p24 from the gag group, p31/32 from the pol group, and any one of the three env proteins, gp160, gp120, or gp41. If a person had gag p24, pol p31/32, and env gp41, let’s say, then their test was Positive; and this was called the FDA criteria for establishing a positive Western Blot.”
Campbell looks at the jury. “Well, that seems simple enough,” and then back to the witness, “and pretty easy to standardize.”
“Yes, but not everyone agreed with these criteria. The Red Cross didn’t for example. They were concerned that these criteria were too limited and would not catch all the blood tainted with HIV; so they wanted something less specific. Plus, there was no proof that the proteins the FDA had chosen were the best ones to represent HIV. So the Red Cross came up with their own criteria, which was one protein from each of the three genes – one gag, one pol, and one env – but without specifying which particular protein in each group. This meant that more people would test Positive, and they could be assured that their blood supply was clean.”
Campbell puts the number 1 beside the gene names env, pol, and gag, rather than checking specific proteins. “So now we have two different groups with two different criteria: The FDA and the Red Cross. Wasn’t that confusing? I mean, didn’t it result in some people testing Positive using the Red Cross standards but not being Positive using the FDA standards?”
“Absolutely. But this is just the tip of the iceberg, because the Centers for Disease Control didn’t like either one of those criteria. The Red Cross was finding far too many Western Blot Positives, but using the FDA criteria, they were finding far too few - less than half of those people already diagnosed with AIDS were coming up Positive, and that was unacceptable if HIV were the cause of AIDS. So they made up their own set of criteria – actually, two new sets. In one case, they tried requiring p24 and one of the env proteins – gp160, gp120, or gp41 – and in the other case they said they just needed two of the env proteins and nothing else – gp41, and either gp160 or gp120.”
“Dr. Tanner, I’m getting confused just listening to you.”
“Imagine the confusion that was created with all these different criteria and no one knowing what was right or wrong. And I’ve just mentioned four out of ten different criteria that are in effect today.”
“Ten?”
“Yes, ten. Different countries have different criteria as well. There is a chart, if that would make it easier to understand.”
Campbell walks over to the large easel and flips to the next page, displaying:
Are You Positive? Page 21