Hearts, Brains, and Minds

by Charles Platt



[olga.jpg]

Olga Visser fields questions at the 1997 Alcor Cryonics Technology Festival. (For more details about the festival, see "Alcor Technology Festival Report" in this issue.) This was Ms. Visser's first public appearance before cryonicists in the United States.

The story of South African perfusionist Olga Visser has become one of the most bizarre episodes in the history of cryonics. It began with an implausible experiment in reversible cryopreservation; it continued with an outlandish claim about a new treatment for AIDS; and it is still not over.

Below is a chronology of events so far, drawn from my own observations and from two sources on the Internet: DejaNews, where all Usenet posts are maintained in a swiftly searchable format, and Keith Lynch's archives of the CryoNet mailing list. I'm especially grateful to Keith for creating and maintaining his web site with such dedication. His URL is www1.access.digex.net/~kfl/les/cryonet/. DejaNews can be accessed at www.dejanews.com/.


[ Note: Since publication the URL for his CryoNet archives has changed to http://keithlynch.net/cryonet/ ]

Note: our publication deadline made it impossible to allow space in this issue for a response from Robert Ettinger, Steve Bridge, Fred Chamberlain, and others who have been involved in the Visser story. We will be happy to publish letters on this topic in our next issue.


Intimations of a Breakthrough

On October 9th, 1995, readers of the sci.cryonics Usenet news group found themselves confronted with a strange report quoted from the South African Sunday Times. Supposedly, a 37-year-old cardio-vascular perfusionist named Olga Visser had developed a new cryoprotectant that would enable human hearts to be frozen with virtually no damage, opening up exciting possibilities in the field of transplants, where organs usually have to be utilized within several hours after removal.

According to the Times Ms. Visser had started her cryoprotectant research two years previously when she helped to establish a heart-valve organ bank. Since valves can be cryopreserved using DMSO, she saw no reason why she shouldn't be able to freeze whole hearts as well. Undeterred by her lack of knowledge of cryobiology, she consulted some experts, read some journals, and formulated her own cryoprotectant.

When she applied it to a pig heart, she reported "no damage" after the heart was rewarmed from liquid nitrogen. She described similar success with human heart tissue. Finally, "a rat heart was frozen, unfrozen, and then warmed by a special process--and started beating. This was the moment of victory for Ms Visser. . . . The little heart beat for 45 minutes before scientists shut it down. They had seen enough."

Ms. Visser was not a doctor or published scientist, but her work was supervised by Dirk du Plessis, the head of cardiothoracic surgery at her hospital; Pierre Cilliers, a biomedical engineer; and Chris Steinman, a physiology professor. This made her claims more plausible--yet CryoCare's president, Brian Wowk, remained skeptical. "This whole South African thing is beginning to sound like a cold-fusion-style PR gambit to drum up research grants and venture capital from naive investors," he wrote in a message to sci.cryonics.

Dirk du Plessis responded via the Net to this and other comments on January 24th, 1996. "The information about the experimentation got out prematurely whilst pilot studies were done," he wrote. He summarized the procedure as follows:

A rat heart beating around the normal rate of 180 per minute is removed and suspended on a Langendorff system. Perfusion commences within 2 minutes. After perfusion with cryoprotectant for approximately twenty minutes, the rat heart is frozen at -196 degrees Celsius by immersion in liquid nitrogen for about two minutes. Rewarming and reperfusion take another fifteen minutes. The heart resumes beating at the same rate as before, and continues to do so for another forty minutes.

According to du Plessis, a paper describing the experiment had been sent to the journal Cryobiology but had been rejected after peer review "for many reasons, but mainly because of incompleteness (which I agree with)."

Still, Ms. Visser's work was a breakthrough, wasn't it?

Well, yes and no. A quick search of the literature showed a couple of precedents. In the June, 1967 Cryobiology a paper titled "Toxicity of High Dimethyl Sulfoxide Concentrations in Rat Heart Freezing" mentioned that when rat hearts were frozen to -20 Celsius with 15% DMSO and later thawed, 80% of the hearts resumed beating. Two years later, the November/December Cryobiology described an experiment by Basile Luyet, who froze pieces of rat hearts in liquid nitrogen after perfusion with 20 percent ethylene glycol, then found that 44% of the pieces resumed rhythmic contractions after rewarming, despite substantial tissue damage.

The real question, though, was was whether Ms. Visser's cryoprotectant could be applied to human beings. This seemed problematic since human organs--especially the brain--cannot be frozen as swiftly as the tiny mass of a rat heart, and her results seemed to be depend on quick freezing.

Still, without additional information no one could be sure of anything.

Unfortunately, according to du Plessis, Ms. Visser refused to give any details about her methodology or the composition of her cryoprotectant until she revised her paper, resubmitted it, and managed to get it published in Cryobiology--whenever that might be. In the meantime, her claims could not evaluated.


The Wild Tirade

Eight months passed without any public statements from Olga Visser. Finally, in August, 1996 she broke her silence in the strangest way. A debate had been raging in sci.cryonics between some cryonicists (including myself and Brian Wowk) and a man named Steve Farmer, who had heard about Paul Wakfer's "Prometheus Project" and suspected that it was a scam.

The Prometheus Project was described in detail, here in CryoCare Report, in our eighth issue. Briefly, the project was instigated in mid-1996 as a first step toward raising $10 million over ten years for an all-out research effort to achieve reversible brain cryopreservation via vitrification.

Ms. Visser entered the online discussion without warning, venting a wild tirade. "Mr. Farmer, you are a man after my own heart," she announced. "Brian Wowk of Cryocare cares not for any any solution to the cryopreservation problem or those of his 'patients' in his care. . . . Let the world know how things are, and who the scoundrels are. Let me start by saying that I have found a way to cryoprotect organs (large and small). . . . Private demonstrations are possible--many have been done. Success rate is far above 75%. I supplied article to 'Cryobiology' for publication in December 1995, and had it rejected for review on three occasions--for minor or irrelevant material." This, she implied, was part of a conspiracy to suppress her work. "I am currently contemplating moving said article to 'Science' as they have no objective interest not to publish. The fact is that my technology is simple, reproducible any not exactly according to all the myths of cryobiology." [sic]

The rambling, incoherent text went on to claim that Ms. Visser's technique would work even if organs were frozen slowly. Therefore, by advocating the Prometheus Project to protect organs via vitrification, Wowk was promoting "a cause that is possibly already won."

The letter continued: "Mr. Wowk, tell me pray--what have you during your entire miserable life ever donated or done towards relieving human suffering?--don't answer. What is your calling to anything of anything?--please answer if you can!"

And it concluded:

"I now have a public statement to make:

"I, Michell [sic] Olga Visser, CEO of Cryopreservation technologies and major shareholder, registered owner of patent pending to successfully cryoprotect organs do hereby declare that Mr Brian Wowk (and any accociated company) is hereby excluded from licencing or any benefit of my technology in future.

"So cryonisists beware where you take your business! ! ! ! ! You might end up in a dead end, and there are some good companies out there. My technology will be make available at a low cost to all other cryonic companies. . . . I have succeeded where all others have failed."

To many readers, this message looked as if it might be a fake. It was riddled with misspellings, and many words were broken by random spaces (removed for clarity in the quotes above). Ms. Visser's own first name wasn't even spelled correctly.

Still, Wowk made a polite reply, and Visser responded--this time, coherently. She stated a personal belief based on "past clinical experience" that it should be possible to cryopreserve any or all organs. The best way to raise money for this work would be by pursuing the transplant angle, because "there is much more profit in organ banks and transplants than in cryonics."

She advised cryonicists: "Entertain and make friends with the press and media above all else--they are more powerful than all governments and academics put together, they get you heard where it counts--the man in the street, and they will advertise what you are doing for cryobiology and suffering patients awaiting a transplant thus attracting even more funding. They also give you the leverage you need when it comes to bureaucrats. Before you know it, cryonics will be as recognized as corn flakes, and you will have achieved your goal."


Rivalry and Politics

Something very strange was happening here. First, Olga Visser had been a perfusionist working on the other side of the planet with no apparent interest in the primarily American field of cryonics. Without warning, she turned into a wildly partisan cryonics activist; and then, just a few days later, she learned to spell and format her text, ceased making wild accusations, and began offering friendly advice.

The mystery was partially resolved on September 8th when an astonishing press release was issued jointly by Robert Ettinger, president of The Cryonics Institute (CI), and Steve Bridge, president of Alcor Foundation. Apparently Ettinger had been in discreet contact with Ms. Visser earlier in the year, had satisfied himself that her work was genuine, and then contacted Alcor. The two groups formed an unprecedented secret alliance, contributing money to Ms. Visser's research and ultimately flying her to Alcor's facility in Scottsdale, Arizona. From August 30th through September 4th she demonstrated her experiment to Ettinger, Bridge, and several officers and directors of Alcor. She also gave CI and Alcor an exclusive license to use her present and future technology for cryonics applications.

Ms. Visser's hostility toward the Prometheus Project now made a little more sense to those who knew the unfortunate history of rivalry afflicting cryonics research.

At this point I must make it clear that I am a biased observer, since I hold shares in 21st Century Medicine, where a lot of research has been done. Also, I have been an outspoken skeptic about Olga Visser's work, I am an ex-Alcor member and a cofounder of CryoCare, and I am the editor of this newsletter. Bearing all this in mind, I will still attempt to summarize the personal relationships between various factions, because they are relevant to the Visser story and the future of cryonics research in general.

Under the guidance of Robert Ettinger, CI has financed Ukrainian scientists who have frozen sheep brains using the same simple protocol that is applied to CI's patients by morticians. Ettinger has claimed that the results of these experiments are encouraging, but Mike Darwin (who has led research efforts at 21st Century Medicine) and several CryoCare members (including myself) have complained that the Ukrainian work is poorly documented and shows severe tissue damage.

Meanwhile, 21st Century Medicine is financed largely by Saul Kent, who earned lasting animosity from several Alcor directors when he agitated for a change of presidency there five years ago. Darwin is also disliked and distrusted by some at Alcor, where he served as a former president and was subsequently head of research. Darwin has a well-known habit of sounding off with a scathing mixture of moralistic disapproval and apocalyptic gloom that some people find quite annoying. He comes across as a smart-ass who finds it hard to resist telling other people (such as Robert Ettinger, or his former coworkers at Alcor) what they are doing wrong.

Since Paul Wakfer has been intimately associated with 21st Century, he is viewed by some as being informally affiliated with the Darwin/Kent "faction," and his Prometheus Project was distrusted by a few activists who wondered if its benefits would be shared equally among all participating cryonics organizations. Meanwhile, on a more personal level, Prometheus looked like another attempt by the Darwin/Kent faction to claim the technical high ground in research and tell everyone else, "Be reasonable, do it my way."

Bearing in mind this depressing legacy of rivalry and mistrust, it was no surprise that Alcor and Robert Ettinger gave Olga Visser such a warm welcome. Ettinger was soon writing a series of messages to CryoNet appealing directly to people who had pledged to support the Prometheus Project. He urged them to take the exact same sum they had pledged to Prometheus and give it to CI, where it would be used right away to extend Olga Visser's research, which had already proved itself by achieving a genuine breakthrough.

This sounded compelling, but did it really make sense? After all, Olga Visser's cryoprotectant had been demonstrated only on rat hearts weighing a few grams, and there was still no evidence that it could be scaled for larger organs. Nonetheless, Ettinger and Bridge seemed quite confident. "There are experimental and theoretical reasons to think the Visser method will work well with brains also," they wrote--although they offered no evidence to substantiate their claim, and indeed the details of Ms. Visser's experimental protocol were still as secret as her cryoprotectant.

The press release admitted that during her demonstrations at Alcor, "several" rat hearts had failed to resume beating, and two had showed only "weak beating" (a term that was not defined). Nevertheless, Ettinger and Bridge insisted that Visser's work was "arguably the most important since 1948, when Jean Rostand froze frog sperm with glycerol." One heart, they said, had showed "strong beating" when carefully rewarmed after immersion in liquid nitrogen.

This immersion had lasted only 30 to 60 seconds, because of "limitations of equipment"--a term that was not explained and was hard to understand, since there is certainly no shortage of liquid nitrogen at Alcor Foundation, and human patients have been maintained in it for decades. Still, Ettinger and Bridge told their readers that according to Olga Visser, in her South African laboratory she had revived hearts after fully 45 minutes of immersion.

What did all this mean to cryonicists? "It seems very possible," said Ettinger and Bridge, "that our cryonics patients will very soon have much better suspensions than any previously available."

The press release was circulated on CryoNet, sci.cryonics, and several medically oriented news groups. But the publicity didn't stop there. It turned out that Alcor had followed Olga Visser's advice to "entertain and make friends with the press and media above all else." They had invited Michelle Boorstein, a reporter from the Associated Press news service, to witness the Visser demo. A couple weeks later, Boorstein's description of the experiment was carried by many major newspapers.

It was an uncritical, lyrical account, prompting one net user to ask how Alcor had managed to secure such favorable coverage. Steve Bridge had an immediate answer: "Few reporters invited to be an insider on something like this are going to turn it into an opportunity for dirt. They want more scoops in the future." He went on: "Once you humanize cryonics, it makes it hard for a reporter to look at it in such a negative light. They may not think it will work, but they admire us for trying to buck the odds."

The story was picked up by serious journals such as New Scientist, where it was augmented with some truly astounding claims. "Visser's team has also revived other rat organs," the magazine stated, "including livers and kidneys. Even rat brains seem to survive freezing unscathed." Where did these claims come from? The only possible source seemed to be Ms. Visser and her coworkers.

Despite her habit of talking freely to the press, however, she still maintained strict secrecy regarding the composition of her cryoprotectant. Thus, it was still impossible for anyone to respond to her public statements. No one could attempt to replicate her work until publication of her paper, which still hadn't been accepted by Cryobiology, Science, or any other journal.


Clinical Trials--with Humans

On September 14th, Brian Wowk pledged $1,000 "toward brain electron microscopy study of the Visser cryoprotectant, provided that CI/Alcor demonstrate in a well-documented experiment that a rat heart can be recovered from -140 degrees Celsius (or lower) with a cooling rate that does not exceed 2 degrees Celsius per hour below 0 degrees Celsius." Wowk still doubted that the technique was scalable for large organs, and he wanted proof.

No one showed any interest in accepting his highly conditional offer. Instead, Robert Ettinger continued campaigning for immediate, unrestricted donations. On September 15th he suggested that such donations would "help in our effort to apply and extend the Visser method THIS YEAR, hence make a very large step forward in cryonics research--possibly even produce superior cryonic suspension for our very next patient (who might be someone you know)."

This was a very surprising statement, since it seemed to suggest that Visser's cryoprotectant, with unknown toxicity or other side effects, might be perfused through a human patient within three or four months. Ettinger was challenged, but remained unrepentant. "There are additional reasons for optimism," he wrote, "which we cannot yet reveal, based on the specific nature of the Visser method and its effects."

Of course, here again there was no way for anyone to dispute his claim because the "specific nature" remained a secret.

Several critics, including myself, voiced persistent pleas for more data. Finally Olga Visser addressed some of the issues. Still without revealing the composition of her cryoprotectant, she said that it had "no known toxic effects" when used according to her protocol. Then she made a strange additional statement: "Toxicity clinical trials with humans for use of the compound as a drug are almost completed here in SA, and results will be made available before the end of this year."

This was even more surprising, since it suggested that she was applying the cryoprotectant to living people. No one challenged her on this publicly at the time, and her message was soon lost amid the constant flow of new information on the net. Less than six months later, though, the real meaning would become apparent, with devastating implications that extended far beyond cryonics.


Secret Compound--Revealed

In the meantime, Ms. Visser echoed Robert Ettinger's request for more funds. "Why donate to CI/Alcor now?" she asked rhetorically, and offered a simple answer: "CI/Alcor have an arrangement and access to all [my] information, past, current and future of our co-operation groups (with respect to cryo). By limiting them [financially] now, because of their contractual restraints you might quite well be limiting yourself or a close friend of a 'better' preservation."

The text was garbled, but the implication was obvious: the secret substance would be imminently available for use in cryonics cases. The only missing ingredient was money.

This raised the interesting question of how much money Ms. Visser herself had already received from Alcor and CI. Alcor's total expenditure on research during 1996 was $48,611, which presumably includes the Visser trials, since they were Alcor's primary research endeavor.

As for the skeptics who still demanded experimental data, Visser had a message for them. One day later, she wrote that "any cryonicist who asks for more information, is 'looking a gift horse in the mouth' so to speak, has an agenda or ulterior motives and obviously does not take their own 'preservation' seriously."

She concluded: "The petty bickering and agenda driven mail [on the Internet] would drive anyone insane, especially if you are expected to respond to it."

And so, for the next three months, she made no further responses at all.

Her self restraint finally broke when she was challenged on a seemingly minor point by Steve Harris, an M.D. and longevity researcher who has advised on many cryonics cases. "If [the rat hearts] beat," Harris asked, "do they beat forcefully enough to mount a blood pressure, or would they just quiver if put under load? I suspect that they beat in coordinated fashion when unloaded. That was what was reported in the news, and that is what makes sense. Heart cells individually isolated in a dish each beat, and when they connect up, they beat in unison, as electrical discharge from one discharges the next one touching it. This happens in a ventricle, too--no conduction system (which is made out of specialized heart cells anyway, not nerves) is required."

Harris added as a PS: "Nerve cells have already been suspended by freezing in liquid nitrogen--that's not the problem. It's doing this to a large connected mass of them that is the problem."

His post seemed polite enough (certainly by Internet standards) and provided some useful information. For some reason, though, it triggered Ms. Visser's flame reflex. "Dr. Steve Harris reminds me of the insurance salesman who believes if he talks fast enough and sounds intelligent, he might be believed," she wrote--without, of course, addressing any of the points in Harris's letter.

She scorned Harris's description of the mechanism of heart contractions and even suggested that he should be disbarred as a doctor. She advocated "some sort of public warning for similar symptoms as those displayed by yourself. I personally suggest a permanent holiday, before you do yourself a permanent injury."

She signed off: "Best wishes, and happy holiday, Olga."

Her next target, on December 3rd, 1996, was Billy Seidel, an amiable CryoCare member who suggested that it would be helpful to have more than the general verbal assurances that Robert Ettinger had been offering. "You pathetic, miserable excuse of an organism," Visser responded to Seidel. "Perhaps Prof. Ettingers' say so does not make it true, but your contention thereof almost certainly does. Rather crawl back in your miserable hole life has provided for worms like you, than insult those who contribute to life what you can never understand, and suffer humanity no more of your ignorance."

Interestingly, though, Ms. Visser did not respond to a far more important message one month later, on January 3rd, 1997, signed jointly by Mike Darwin, Steve Harris, and Brian Wowk. It included the offhand statement: "Even the Visser agent (dimethyl formamide) and other peralkyl-amides, while more penetrating than glycerol, were found to be intensely hemolytic (membrane toxic) at vitrifiable concentrations. (Peralkylamides were also found to be poor cryoprotectants at lower concentrations, including 25%, in a variety of relevant systems.)"

The context was unappetizingly technical, certainly a lot less fun to read than Ms. Visser's bizarre diatribes, but the content was surely sensational. Either the smart-asses at 21st were bluffing, or they had somehow unearthed Olga Visser's biggest secret: the composition of her wonder drug. Worse still, they were casually claiming that it belonged to a class of substances that were known as cryoprotectants--and didn't even work very well.

Net users waited for some response. Another wild, raving denunciation from Visser? A calm denial from Alcor? A refutation from Ettinger?

Nothing happened. There was no answer at all, which seemed to suggest that the people at 21st had identified the cryoprotectant correctly. And if that were true--why, Visser's drug was no big deal after all. It certainly wasn't likely to revolutionize cryonics, because it had already been tested and rejected by scientists who had the experience in cryobiology which Olga Visser lacked.


Next: a Cure for AIDS?

On January 24th, 1997, net users were amazed to read a message on CryoNet reporting a completely new and far more outrageous claim emanating from South Africa. According to newspaper reports, Ms. Visser had moved from reversible cryopreservation to the cutting edge of pharmaceutical research. Somehow she had arranged a private audience in front of the South African cabinet, including Nelson Mandela. With her she presented some AIDS patients whom she had injected with a new drug that she had formulated, code-named "Virodene."

The patients reported that they had been helped by the drug. Many of their symptoms had vanished. Their T-cell counts were higher. "The scientists and some of the volunteer patients said they believe the research gives rise to fresh hopes that a cure for AIDS might be found before the turn of the century," reported the Zaire Mail & Guardian, which added that "the researchers received a standing ovation from the Cabinet after the presentation."

Based on new information provided by Ms. Visser and her coworkers (one of whom, once again, was Dirk du Plessis), the newspaper claimed that "Virodene kills the Human Immunodeficiency Virus in the body and allows people infected with HIV to live a long and normal life. One of the most dramatic trial results was that Virodene could apparently even pull full-blown Aids sufferers back from the brink of death, reverting their condition to that of HIV-positive, in terms of which they are no longer so susceptible to opportunist diseases."

Ms. Visser wanted $800,000 from the South African government, to continue her work. While she was waiting for the money, she had evidently followed her usual practice of feeding information to her friends in the press.

This time, though, she was dealing with a much more sensitive topic than cryo-preservation. Within a matter of days the journalists turned against her. "Scientists and AIDS groups reacted with shock and skepticism," reported the Associated Press. "They denounced the trio for not following standard research practices, such as subjecting their work to peer review, and also for conducting human trials apparently without approval."

In fact, Ms. Visser hadn't bothered to get permission from anyone before she started experimenting on human patients, and there was some question whether the patients knew enough about "Virodene" to give informed consent. Indeed, no one knew what "Virodene" consisted of, because its composition was secret, rousing an ominous sense of deja-vu among cryonicists. Worse still, according to the Associated Press report, "Visser said she discovered the anti-viral properties of Virodene while conducting cryo-preservancy experiments."

Did this mean that "Virodene" had been developed during the "toxicity clinical trials with humans" that she had written about online? In that case, could it really be true that "Virodene" and the rat-heart cryoprotectant were the same drug?

Early in February, these fears were confirmed. The South African Medicines Control Council banned further use of "Virodene" on human patients because it had been found to contain "a highly toxic industrial solvent, dimethylformamide (DMF), which can cause fatal liver damage and has been linked to the development of cancer."

If DMF was such bad stuff, why had it made the AIDS patients feel better? Probably they enjoyed a short-term benefit at the expense of longer-term survival. DMF attacks the body's immune system, which isn't a great idea for AIDS patients; but simple immune suppressants such as prednisone and cyclophosphamide have a similar effect and are known to produce transient feelings of wellbeing even while they cause biological damage. Ms. Visser and her associates were probably unaware of this, since they lacked prior experience in the field.

Steve Harris, still irked by Visser's suggestion that he should be disbarred as a physician, wrote a scathing denunciation on CryoNet. "Yes, dimethylformamide is a mutagen," he stated, "with a great deal of toxicity for multiple organs. Once upon a time, it was tried out as a chemotherapeutic agent. Gram for gram, it's about as toxic as ethylene glycol or methanol, and far nastier to the germ line (reproductive) cells than either of these. All of which caused us at 21st Century Medicine some consternation some time ago when Visser announced that her cryoprotective agent was being tested in humans, and was without significant toxicity."

Harris continued: "Only a damn fool would give something with this record of toxicity to human beings with AIDS, without a huge amount of published and verified research of the effects of this substance on HIV replication in vitro (in culture), plus confirmatory research on its effects on closely related lentiviruses such as FIV and SIV in animal models (cats and monkeys). Where is all of this research? It certainly isn't turning up on my computer searches of the world medical literature."

This seemed a clear and chilling refutation, yet Visser's rat-heart experiments had roused a lot of hope among some cryonicists, and they weren't going to give up easily--especially since they had an instinctive sympathy for anyone who defied the authorities. "I am not saying in this post that the Visser reports are true, accurate or right," said one British subscriber to CryoNet, "but that they deserve consideration and time should be given for the story to properly emerge and all sides be heard in a civilised manner. Leave policing of medical procedures and human rights to the South African authorities. I would like to end this message by asking Olga Visser to put her side of the recent events to this forum so we can get a more balanced view and not just a hysterical media view."

Olga Visser's husband, Siegfried, responded: "As far as the AIDS furore goes, some information leaked prematurely to the press."

It was deja-vu all over again, recalling du Plessis' statement about the rat hearts a year earlier, where he claimed that "the information about the experimentation got out prematurely." Those pesky reporters! How did they keep finding out about these things?

Siegfried Visser continued: "No human rights were violated at any stage. Our trials have been suspended for ten days, in order to give the MCC [Medicines Control Council] time to verify our results. They acted under pressure from the established AIDS research groups, and not from any of our patients, who support us all the way. We are not being investigated, and no charges can or will be brought against us."

And so, clearly, in the world according to Visser, there was still no problem, no shred of self-doubt. The AIDS drug was a miracle treatment and was merely being suppressed by jealous "establishment" scientists. The cryoprotectant likewise was still the greatest breakthrough in thirty years, even though it turned out to be the same drug, a well-known compound that was well understood and not especially effective.

But Siegfried Visser still refused to confirm or deny that the drug consisted of DMF. That didn't stop him from threatening to sue people (such as Saul Kent) who had stated publicly the composition of the cryoprotectant, because they had opened the door to "possible miss use of the inn correct drug or dosage by desperate 'net surfer AIDS patients' or subsequent information, the total of which we hold Mr. Saul Kent et at personally responsible and liable." The incoherence of this threat was eerily similar to the wild invective that had appeared previously under Olga Visser's byline; but once again, the meaning was clear enough.

Meanwhile, coincidentally, Ms. Visser was scheduled to appear at the 1997 Alcor Cryonics Technology Festival. Many activists had registered to attend this event, including Paul Segall of BioTime (a highly successful startup company that has conducted cryopreservation research), Thomas Donaldson (a scientist who has written extensively about life-extension drugs), Ralph Merkle (a world expert on nanotechnology), along with Robert Ettinger, Steve Bridge, Mike Darwin, Saul Kent, other personnel from 21st Century Medicine, and myself.

Some of us wondered if Ms. Visser's problems in South Africa might prevent her from showing up; but at 9:45 AM on Saturday, February 1st she stood in a hotel conference room in Scottsdale, Arizona, ready to answer questions from the audience.


To Beat or Not to Beat

[audience.jpg] [Photo Caption]
An audience at the Alcor facility waits expectantly on February 2nd, 1997 to see whether a rat heart perfused and frozen by Olga Visser will resume beating after it has been rewarmed. The experiment is being displayed on a large video monitor (beyond the edge of this photo).

Ms. Visser is slim and stylish, and presented herself with a compelling mixture of energy, and sincerity, and vulnerability in marked contrast with her belligerent, incoherent rants on the Internet. "A lot of people probably thought I'd ride in here on a broom," she said with a gentle smile. She assured the audience that she is a shy person who dislikes confrontations. In fact, she claimed that her combative messages were actually written by two other people: her husband, Siegfried, and an employee of the South African Government who protects her from her critics and keeps her away from journalists.

In the near future, she said, she plans to cryopreserve a pig heart, keep it in liquid nitrogen for a few days, then rewarm it and transplant it back into a pig. Since she belongs to a department of cardiovascular surgery, she is not allowed to work on any organ other than hearts, but she reiterated her claim that there should be no problem scaling her protocol to cryopreserve large organs such as the human brain, and she endorsed the general concept of cryonics.

She finished with a telling self-description. "If I want to do something," she said, "I do it. I go against most other people, I'll just go ahead and do it, in any country, and then I'll answer questions afterward."

Her question-and-answer session was only a brief part of Saturday's program at the technology festival (which is reported elsewhere in this issue of CryoCare Report). The next day, though, Ms. Visser was the solo attraction as she attempted to demonstrate her cryoprotectant in the Alcor facility in front of an audience of conference attendees. By 10 AM she was hard at work perfusing a fresh rat heart at a small lab bench while Alcor's Hugh Hixon sat on one side of her and Fred Chamberlain recorded her work via a video camera less than eighteen inches away.

The heart was attached to a cannula at the bottom of a glass column containing Ms. Visser's cryoprotectant at a temperature close to freezing. A mixture of 95 percent oxygen, 5 percent carbon dioxide was bubbled through a small reservoir of the solution; from there it perfused the heart by force of gravity. A Langendorff unit maintained temperature; a thermocouple immersed in a small cup around the heart transmitted data to a nearby PC running standard lab software that displayed realtime temperature graphs.

[ratliver.jpg] [Photo Caption]
Olga Visser (left) applies a thermocouple probe to a fragment of rat liver that she test-froze for one minute in liquid nitrogen, to verify that its temperature fell to -196 degrees Celsius. Mike Darwin (center) and Mary Margaret Glennie (left) observe, at the Alcor Technology Festival.


By 11 AM thirty visitors had gathered in an adjacent room, where a large TV showed excellent close-up pictures from Fred Chamberlain's camcorder. Attendees were allowed to make brief personal visits to the lab area, and photographs were permitted without any restrictions. This free access was extremely welcome after more than a year of secrecy surrounding Ms. Visser's protocol.

She worked with swift, intent motions, sometimes standing, sometimes sitting in front of the metal rack supporting the laboratory glassware. She perfused the heart for about half an hour at a temperature between 1 and 2 degrees Celsius, ramping up in three stages from a relatively weak concentration to a final value of 20 percent. She then disconnected the heart from the cannula, wrapped it in cotton balls, and placed this mass in a thin-walled plastic cup (similar to little cups that contain dairy creamer in restaurants). The cotton was soaked in cryoprotectant. A rubber band was stretched around the mouth of the cup, and the cup was then placed in some Dacron wool inside a Coke can from which the top had been removed. This, according to Ms. Visser, was her way of simulating a cryonics patient being placed in a dewar.

The Coke can was dunked in a real (small) dewar of liquid nitrogen. Normally Ms. Visser freezes a heart for no more than 60 seconds, because (she claims) she is so impatient to see it beat again. Some observers were skeptical that this was long enough to reduce the heart's temperature to -196 Celsius, especially since the water in the cryoprotectant solution saturating the cotton balls would inevitably liberate heat during the freezing process.

In order to satisfy the skeptics, Ms. Visser agreed without hesitation to freeze the heart for as long as 20 minutes. She seemed absolutely confident that this would make no difference to the outcome of her experiment.

Several observers verified that the Coke can was, in fact, totally immersed in liquid nitrogen. After 17 minutes, it was removed. The frozen cotton mass was placed in a concentrated solution of the Visser cryo-protectant, where it resided for about ten minutes before she started prying the cotton away with tweezers. About another ten minutes later the heart was revealed, and was a healthy red-brown color. She reattached it to the cannula by its aorta and recommenced flowing cryoprotectant solution through it, gradually warming it to room temperature.

This, of course, was the moment everyone had been waiting for. While conference attendees watched impatiently, Ms. Visser tapped the heart, shook it, prodded it, massaged it, and forced additional fluid through it under high pressure from a large syringe. Finally she pierced it with three EEG probes whose signals were displayed on a CRT screen mounted in a unit that emitted audible beeps.

The beeps, however, were erratic and seemed to be generated each time the assembly was moved or shaken. When Ms. Visser allowed the heart to dangle undisturbed from its cannula, the beeps settled into a steady rhythm--which coincided precisely with drips of cryoprotectant falling from the bottom of the heart, and seemed to be caused entirely by associated fluctuation in conductivity. Ms. Visser suggested that the heart was pumping the cryoprotectant through it, but no contractions were visible.

Undaunted, Ms. Visser walked into the other room and told the audience that the beeps indicated weak ventricular contractions. This was politely disputed by two attendees, one of them with formal training as an EEG technician. Observers also noticed that the heart had lost its healthy color and had turned gray after being warmed to room temperature. This blanching indicated typical post-freezing injury, and the resistance to free flow of fluid through the heart suggested that the capillary bed had been damaged by freezing. This was confirmed a little later when, with reluctance, Ms. Visser allowed the heart to be cut open.

[rheart2.jpg]
[Photo Caption]
Olga Visser supervises the perfusion of a rat heart with her secret cryoprotectant at the Alcor Foundation, while Fred Chamberlain focuses his camcorder. The heart is in the styrofoam cup at center. The large object at right is the Langendorff unit. The video monitor displays temperature graphs.
[rheart4.jpg]
[Photo Caption]
At the Alcor Technology Festival, Olga Visser stands beside a video monitor displaying equipment in the next room. Her claim that a rat heart resumed beating, on February 2nd, 1997, was disputed and was subsequently withdrawn.

Even Ms. Visser's supporters were forced to admit that this heart had not, in fact, resumed beating. She still seemed unworried, however, and and promptly set to work on another rat. Since the full cycle of dissection, perfusion, immersion, and reperfusion would take another two hours, entailing long periods of no visible activity, visitors started wandering freely around the Alcor facility, and the event started to resemble a friendly, non-alcoholic cocktail party.

Alas, the second heart of the day was even less successful than the first. It failed almost completely to reperfuse, and one observer judged that it was grossly edematous. At this point many observers gave up and left, but Ms. Visser continued resolutely with a third heart--which also failed to resume beating when it was rewarmed in the late afternoon.

She took a break at this point, but returned around 7:30, ready to make one last attempt. By this time the audience had shrunk to only seven visitors: Mike Darwin, Sandra Russell, and Joan O'Farrell (all from 21st Century Medicine), Erico Narita, myself, and two others. Alcor personnel Hugh Hixon, Fred Chamberlain, Linda Chamberlain, and Steve Bridge were also present.

The fourth heart was a problem even before it was frozen. For reasons that no one could determine it perfused extremely slowly, as if it contained some kind of interior obstruction. This time Ms. Visser wrapped it in a thicker layer of cotton (by my visual estimation) and immersed it in liquid nitrogen for only four-and-a-half minutes. To no avail: the heart showed significant cracks when it was removed from its cocoon, and was clearly damaged beyond repair.

Ms. Visser shook hands all around, we thanked her for her efforts, and the great rat-heart freeze-in was over.


Conclusions

Absence of evidence is not, as the saying goes, evidence of absence. The failure of four trials does not prove that Ms. Visser's cryoprotectant is useless, especially since there are reports that on other occasions she has been successful.

On the other hand, the trials provided a sobering view of Ms. Visser's experimental technique. She worked impulsively, changing parameters like a chef deciding to add a little more salt or a little less sugar each time she cooks a particular dish. The final concentration of her solution was 25 percent during previous trials; at the public demo, for reasons unspecified, the concentration was 20 percent. The procedure for wrapping the heart clearly varied from one trial to the next, and the Coke can was pre-filled with liquid nitrogen during the second trial, but not during the first.

There seemed to be no standardized written protocol for mixing, filtering, and storing chemicals, cleaning equipment, and handling the solution. The weight of each donor animal and each heart were not recorded, even though heart mass varies widely among rats. The quantity of cotton wool wrapped around each heart was not measured; nor was the volume of cryoprotectant that presoaked the cotton. This latter variable was crucial, since each gram of water in the solution would release 80 calories when frozen.

None of the hearts was fitted with probes to measure temperature during immersion, although this would seem to be a basic, fundamental, and obvious necessity. Also, since the Coke can containing the heart tended to float, there was an obvious need for some simple mechanical apparatus to control immersion, especially since dense clouds of vapor made it almost impossible to view the can during the first minute or two. Observers tend to become inattentive during a number of long, unsuccessful trials, which raises the possibility that during some of Ms. Visser's previous demonstrations the hearts were not in fact properly immersed and consequently may not have been completely frozen.

There was no permanent record (other than shaky video) of EKG signals from the rewarmed heart, and there was no one affiliated with the experiment who had necessary training to evaluate the EKG.

Most troubling of all was Ms. Visser's initial claim that the first heart in the series was a success. Of course, she was operating under considerable pressure in front of an audience containing many skeptics, and she must have felt a great need to vindicate her procedure. Still, she did make a false claim, which must raise suspicion that she cannot be trusted as an objective observer.

[rheart3.jpg]
[Photo Caption]
Hugh Hixon places a rat heart in a dewar of liquid nitrogen , assisted by Olga Visser.
[rheart1.jpg]
[Photo Caption]
Closeup of Olga Visser's perfusion equipment at Alcor. Tubes feed cryoprotectant to the rat heart in the styrofoam container.

Aftermath

On February 1st, Steve Bridge made a scheduled departure as president of Alcor and Fred Chamberlain (one of the founders of Alcor) took his place. Almost immediately, on February 3rd, Chamberlain made a surprising and disarmingly honest revelation: Alcor had conducted its own trials of Olga Visser's procedure on numerous occasions during the previous six months, and had been unable to revive a single rat heart, even using the same batch of cryoprotectant that she had originally imported from South Africa.

Chamberlain wasn't ready to give up. He suggested that the cryoprotectant might have become contaminated by "breakdown products" during storage. Still, he is a scientist (he used to design unmanned spacecraft at the Jet Propulsion Laboratory) and he has a scientist's concern for data. Clearly, if the data weren't there, he wasn't willing to make any more optimistic statements about Ms. Visser's work.

He wrote: "After a fresh supply of the Vissers' cryoprotectant is obtained from the Vissers' source in South Africa, we will repeat the experiment using it, and report the results, positive or negative, on CryoNet. If at that point, an encouraging result is obtained, we will attempt to reach a point where a reliable demonstration can be produced in a high percentage of the attempts. Otherwise, we may have to conclude that this approach lacks sufficient promise to warrant further effort at this time."

His style was calmly factual, but the message was grim. Olga Visser's protocol was being allowed one more chance. If that didn't work out, Chamberlain seemed to be saying that Alcor would simply abandon it.

Robert Ettinger, however, was still cautiously optimistic. He quoted observations from CI's Andy Zawacki, who had witnessed a successful rat-heart demo. "Though there was some concern that the heart was not fully immersed in liquid nitrogen for the final 30 seconds," Zawacki wrote, "it appeared to me, considering the way liquid nitrogen boils, that it was covered." And Ettinger appended his own comment: "Andy has a lot of experience in viewing things in liquid nitrogen under a variety of conditions."

Chamberlain, however, wasn't willing to allow this vague reassurance to survive unchallenged. He responded: "A review of a videotape of this run has showed that full immersion was not accomplished. A lot of vapor was emitted, and this may have made it difficult even for those close by to be sure of the level. The videotape, on the other hand, shows the upper part of the shroud being out of the liquid nitrogen for the entire period of exposure."

He continued, with relentless precision: "After removal from liquid nitrogen, there is (that is, the videotape shows) a boundary line about half way down the shroud. Below that line, the surface is dull white and dry looking, an indication that the surface photographed was solid. Above that line, there is a different, glistening surface. It seems unchanged from the appearance just prior to exposure to liquid nitrogen."

None of Visser's supporters answered this message. Indeed, messages of this kind have never been popular in cryonics. They dash our hopes and remind us of our limitations--and our impending demise.


Science vs. Faith

Cryonics was created in a spirit of rebellion by people who refused to accept orthodox ideas about the inevitability of death. Cryonicists also tend to distrust authority, and their lust for life gives them a powerful incentive to believe anyone who brings encouraging news, regardless of whether the message comes from a bona-fide scientist such as Eric Drexler or an uncredentialed investigator such as Olga Visser. To many cryonicists, formal qualifications are irrelevant or even a cause for suspicion, since they sustain an institutional elite that seeks to protect its turf from outsiders with radical ideas.

This, I believe, helps to explain the antipathy between Alcor/CI, on one side, and 21st Century Medicine on the other. The smart-asses at 21st have complained repeatedly about unprofessional research and unreliable data. Worse still, they've made some disturbing allegations. Mike Darwin, for instance, has been fond of reminding people that cryonics, as practiced today, is not only error-prone but may be severely injuring many of its patients.

Where have cryonicists heard this kind of talk before? Why, from cryobiologists! In fact, by speaking out against their own little community, researchers at 21st effectively affiliated themselves with the enemy, the "properly qualified" naysayers of the scientific elite, those maddening experts who appear on TV programs, mocking the whole idea of human cryopreservation.

By contrast, Olga Visser was the kind of personality whom cryonicists could identify with, a character straight out of a novel by Robert Heinlein or Ayn Rand, sneering at the experts and following her own defiant path. She was an unqualified outsider, working against difficult odds--just like most cryonicists! Better still, she showed that the smart-asses were wrong. Science didn't have to be so complicated after all.

Alas, almost always, science is complicated, and there are few shortcuts. Simplicity is the stuff of science fiction or pseudoscience; and when pseudoscience competes directly with science, the outcome is inevitable. If some dreams are crushed in the process, this is the price we pay for allowing ourselves to move from a position of skepticism to uncritical faith. There is a fine line between cryonics and religion; both offer the hope of renewed life, and neither can be proved or disproved. To cross that line is a constant temptation; but we endanger the serious status of cryonics, and hence our own survival, if we yield to that temptation.

Olga Visser's brief passage through cryonics could still turn out to be a positive, salutary event if it reminds us to be more circumspect in the future. The next time a character out of a Heinlein novel turns up with a secret formula to fix our deepest fears, we may be a little less willing to pay cash for the recipe. We may even be a little more tolerant of the smart-asses who insist on reminding us that death is not an easy adversary, human biology is infernally delicate and difficult to preserve, and scientific rigor is a fundamental necessity, not a tiresome detail.

In the meantime, Olga Visser's attorneys have advised her to say nothing about her AIDS experiments, her paper describing her cryoprotectant still hasn't been accepted by Cryobiology or Science, and although she has claimed that the properties of her cryoprotectant have been replicated by other researchers, she has not cited any publications reporting their work.





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