Cort Johnson reports: Ian Lipkin: Three to Five Years* to Solve Chronic Fatigue Syndrome (ME/CFS)  December 26, 2015

Ian Lipkin flew to Lake Tahoe this December to fundraise for joint projects with Simmaron Research Foundation. In a talk covering his virus hunting career, the threat of pathogens to humanity, and his work with chronic fatigue syndrome (ME/CFS), he dropped a bombshell:  he stated that he believes it’s possible to solve ME/CFS in three to five years.

On that hopeful note, let’s learn more about Dr. Lipkin, his work, and his collaborations with Simmaron.

Dr. Peterson’s Introduction

Lipkin’s Columbia Center for Infection and Immunity (CII) has established close ties with the Simmaron Research Foundation. Only a couple of months before, his chief collaborator, Mady Hornig (and Simmaron Scientific Advisory Board member) had given a talk.  Now Ian Lipkin was here.

Tea-Time at Simmaron I: Mady Hornig on the “Peterson Subsets”, Immune Exhaustion and New Gut Findings In ME/CFS

Dr. Peterson started his introduction of Ian Lipkin by noting that he’d known him since they crossed paths in the 1980’s when Dr. Peterson sent him patients suffering from HIV/AIDS.

Ian Lipkin was the first to isolate Borna disease virus. He identified the West Nile Virus, developed technologies to identify SARS and then hand carried 10,000 test kits to Beijing at the height of the outbreak. He most recently discovered a highly dangerous virus that recently jumped into humans called MERS (Middle Eastern Respiratory Syndrome Coronavirus).

Lipkin has pioneered many technological breakthroughs in finding pathogens including the use of MassTag-PCR, the GreeneChip Diagnostic, and High Throughput Sequencing. His latest breakthrough is the development of a new screening technique that enhances researchers ability to find viruses 10,000 fold.

Called the top virus hunter in the world, Ian Lipkin runs the Center for Infection and Immunity at Columbia, and is the director of the Center for Research in Diagnostics and Discovery (CRDD) at the NIH. He also worked closely with Steven Soderbergh on his film Contagion.

Ian Lipkin talks

Who says brilliant scientists can’t be a hoot to listen to as well?
Ian Lipkin’s presentation was both enlightening and at times hilarious. Exhibiting a wry sense of humor, Lipkin poked fun at himself and virtually everyone around him.

The last time he was in Lake Tahoe, he said, was in 1984 and he hearkened back to the HIV/AIDS patients Dr. Peterson sent him in the early 1980’s.

“When you come to a fork in the road – take it!”

He stated the guiding principle in the search for pathogens could be summed up by the great Yogi Berra’s adage “When you come to a fork in the road – take it!”.

HIV/AIDS was the beginning of many changes. Even after the medical community knew it was being passed in the blood it still took them 2 1/2 years to find it. Why did they know a pathogen was present?  Because of the infectious nature of the spread of the disease and the cytokine abnormalities found.

In a Discover interview,  Lipkin noted that he ran the first clinic in San Francisco that would treat HIV/AIDS (then called GRID) patients with neurological problems. (Note the iconoclastic element to Lipkin that showed up early in his career: he was willing to see patients others wouldn’t see. Check out Lipkin’s fascinating story of how HIV/AIDS lead to him to study infectious diseases.)

Lipkin then worked on a virus which demonstrated the effects a persistent viral infection can have on the central nervous system. The virus alters how nerve cells work but doesn’t kill them.

Next, in another story with possible overtones for chronic fatigue syndrome (ME/CFS), he investigated patients who’d come down with what appeared to be a mysterious psychiatric disorder. It took him two years but using a new method involving genetic cloning he uncovered the Borna disease virus. It was the first virus discovered using genetic means.

The Borna virus discovery was a game-changer for pathogen community.
Jump forward thirty years (after it took the medical community almost three years to find HIV) and viruses are being discovered using molecular means all the time. The Center for Infection and Immunity itself discovered 700 new viruses from 2009-2015.

Lipkin was aware of and interested in ME/CFS in the eighties but there was no money. In 1999 he and Britta Evangaard found no evidence of the Borna disease virus in ME/CFS. From there we jump forward to 2010 when NIH Director Francis Collins tasked Lipkin to determine if a retrovirus, XMRV, was present. XMRV turned out to be a laboratory artifact, and the paper was retracted – something that Lipkin said was not all that unusual in science. (He emphasized that he and Dr.
Peterson were very careful to put out studies that would stand the test of time.)

The XMRV discovery tanked but proved to be a boon for ME/CFS by heightening the attention around it. Lipkin had kept an eye on ME/CFS for years and after being hired by the Chronic Fatigue Initiative to take it on, he was back in a big way.

In the next portion of his talk he turned to viruses and humans.

Viruses and Humans

How are most viruses getting into humans? From animals. After it’s jump from primates to humans, HIV is, of course, the most familiar example, but viruses are also escaping from bats, birds, pigs, rodents, insects and even camels into humans.

A sea change in the viral field occurred in 1999 when a mosquito-borne virus – the West Nile Virus – was so bold as to attack the residents of the New York. Lipkin shifted his work from the West to East coasts and ultimately identified the virus. As the outbreak spread, it got the attention of Senator Joesph Lieberman who sponsored the first big initiative to learn how viruses spread from animals to humans.  Politicians, Lipkin said, can be very important allies.

If viruses are going to get spread around the world, New York City may very well be the best place to do that. Twenty-one million passengers traveling to and from 72 countries pass through New York airports every year. Animal products including bushmeat – all potentially contaminated with nasty viruses – pour into New York City regularly.

How many viruses remained to be discovered? A survey of one species of bats found fifty-five viruses, fifty of which were new to science.
Lipkin estimated 320,000 viruses were still unknown. He then covered virus’ able to escape from bats, ticks  and rats into humans.

Bats – Called in to investigate an ill Saudi Arabian man (with four wives), he uncovered a new virus called MERS (Middle East respiratory syndrome coronavirus) which was similar to those found in bats. (Asked if there were any bats in the area, he was told no. The next video showed bats flying every which way in the area :)). If the bats weren’t biting the humans, though, how was the bat virus jumping into people?

MERS appears to have been present in bats for quite some time. It spread to camels in the 1990’s and then jumped from camels to humans around 2010.

MERS is not particularly easy to transmit but when it gets transmitted, watch out. Death rates are high. It took one Saudi Arabian to spread MERS to South Korea this year where it killed several dozen people, put several thousand into quarantine and basically threw the country into a panic. Schools were closed, tourists stopped coming, and parts of the economy slumped as South Korea fought off the virus. MERS is the kind of virus that keeps public health officials up at night.

It’s not surprising that Lipkin is wary of pathogens. He noted that he rarely shakes hands but darting a glance at Dr. Peterson said he’d made an exception that evening. (If you haven’t seen Steven Soderbergh film “Contagion” and can handle apocalyptic scenario’s you might want to give it a try. Lipkin consulted extensively on the movie which involved a worst-case scenario of a virus wiping out much of humanity. The film was praised for its scientific accuracy. (Spoiler alert – we do survive in the end :)).

Ticks –  Lipkin believes chronic Lyme patients who are not recovering from antibiotics probably got another infection from the ticks. Lipkin found that over 70% of the Ixodes scapularis ticks associated with Lyme disease carried at least one pathogen and 30% carried more than one in New York. Last year he identified a rhabdovirus (Long Island tick rhabdovirus) new not just to ticks but to science itself. A small survey suggested that 15% of residents may carry antibodies to the virus.

Rats- Lipkin’s study of New York City’s second most common resident – rats – revealed they carried an amazing array of pathogens including Escherichia coli, Clostridium difficile, and Salmonella enterica, Bartonella spp., Streptobacillus moniliformis, Leptospira interrogans, and Seoul hantavirus.

Lipkin is understandably wary of pathogens. He noted that he rarely shakes hands but darting a glance at Dr. Peterson said he’d made an exception that evening.

Later Lipkin referred to the hamburger and French fries lunch that he and Peterson usually have saying do as we say not as we do. How does Lipkin reportedly like his meat? “Burn it” he tells the waiter. The man is taking no chances – he knows too much.

Infection and Disease

A pathogen is just one of the players, however, in a vast swirl of factors which ultimately determines whether one is going to have a chronic illness. Timing, for instance, is a key factor. If you expose a mouse to a pathogen at one stage of pregnancy, it’ll stop moving around its cage. If you expose the same mouse to the same pathogen later in pregnancy, it will run round and around its cage unceasingly.

A large autism study underscored the complex role timing plays. The 120,000 person autism birth cohort study found that if a mother comes down with a fever after the first trimester, her chances of giving birth to a son with autism go up three-fold.  If she treats the fever with acetaminophen, her chances of giving birth to an autistic child drop significantly.  If she takes acetaminophen for any other problem than a fever, her risk of giving birth to an autistic child goes up again.

Three to Five Years – An ME/CFS Timeline

How does all this relate to ME/CFS? Likpin cited the findings of their work to date.

• The suspected pathogens don’t appear to be the problem (the CII is reportedly looking further at herpesviruses.)
• Evidence suggests altered microbiomes (gut flora) are present
• Striking differences in immune expression between shorter and longer duration patients appear to be present
• Preliminary evidence suggests that levels “X” and “Y” metabolites and, at least, one immune protein are significantly altered in ME/CFS.
  (Lipkin embargoed this information pending publication of the paper.
  One of them is highly unusual.)

Lipkin emphasized, though, that ME/CFS is not a one-size fits all disease. For instance, it’s possible that fungi may be a problem for some patients. That’s an intriguing idea given the recent fungi funding in Alzheimer’s disease published in Nature.

Then Lipkin made his bold declaration “We’re going to solve this in three to five years”, with a big proviso. Provided the resources are made available, he believes science can crack ME/CFS fairly quickly.  That sounds really fast, but Lipkin’s time-frame is not that far off from Ronald Davis’s 5-10 time-frame (provided he gets the resources as
well.) (or Dr. Montoya’s).

These eminent researchers believe that given the technology present today we could understand ME/CFS fairly quickly – if enough resources were brought to bear.  Lipkin pointed to a slate of researchers in his lab working on ME/CFS to signify the major shift that’s occurred. He said “I couldn’t have gotten them five years ago”.

He highlighted two places the patient community can make an impact:

• Funding Pilot Studies –   The community can fund pilot studies
  which can be turned into big grants
• Advocacy – Lipkin is a savvy researcher. He knows how the NIH works and once again he emphasized the need for the ME/CFS community to push harder legislatively – to talk to their representatives in the House of Representatives, in particular – and get them to push the NIH for more funding.

Lipkin’s Bucket List

Ian Lipkin has clearly developed a special relationship with ME/CFS, Dr. Peterson, the Simmaron Research Institute. He hadn’t been in the Lake Tahoe area for decades, yet he and two of his assistants had flown across the country to support the Simmaron Research Institute’s spinal fluid work. He was even shaking hands.

I shook my head – not for the first time – about Lipkin. How had we gotten so lucky? Lipkin oversees the work of 65 researchers in the U.S. and 150 more across the globe. The New York Times reported that on any given day his lab had 140 viral research projects underway. The head of the National Institute of Allergy and Infectious Disease, Anthony Fauci said, “Lipkin really stands out from the crowd.”

Yet, here he was in Truckee in mid-December exhorting the audience to support an important Simmaron study that he believed needed funding.

What had driven the “The World’s Most Celebrated Virus Hunter” to take on our disease? I asked his assistants. They told me that Ian Lipkin wants to do two things more than anything else before he retires: he wants to solve ME/CFS, and he wants to solve autism. We’re on his bucket list.

That floored me even more (:)) so I asked – but, but…..doesn’t  he care what other people think about this neglected disease? That question left them almost gasping for breath. After they had been able to calm down, they assured me: no he doesn’t.

The Simmaron Research Foundation’s Next Spinal Fluid Study

Lipkin was at the event to support the Simmaron Research Institute’s next spinal fluid study. The results of the first one – the most extensive spinal fluid study ever done in ME/CFS – were eye-opening. A comparison to multiple sclerosis (MS) found evidence of immune dysregulation almost equal to that found in MS. The difference was that instead of being raised, the cytokine levels were reduced in ME/CFS.

For more on the Peterson’s subsets and Lipkin and Hornig’s Simmaron Work

That finding surely left a big smile on Lipkin’s and Hornig’s faces.
Earlier they had found evidence of a profound reduction in immune functioning in the blood of later-duration ME/CFS patients. Now a similar reduction was found in their spinal fluid. Having findings in two different systems match has rarely happened in ME/CFS. That suggested they were uncovering system-wide problems.

No wonder Lipkin was eager to begin a new and larger spinal fluid study. It’s part of achieving his bucket list.

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