Simon McGrath reports on Dr. Lipkin’s talk to patients in London …

In a talk to patients in London on 3rd September, Dr. W. Ian Lipkin described the extraordinary lengths he and his team are prepared to go to in order to track down the source of an illness, with examples ranging from autism to the strange case of Kawasaki disease.

His talk emphasised the use of high-tech methods and following the evidence wherever it leads, before outlining his ME/CFS research programme that takes a similar approach. And he believes the action in his field is moving from acute illnesses such as SARS to chronic illnesses – including ME/CFS.

Lipkin is a renowned virus hunter who heads up the Center for Infection and Immunity at Columbia University. He’s discovered over 400 viruses, pioneered new molecular techniques for identifying pathogens, and helped the World Health Organisation and Chinese Ministry of Health deal with the SARS outbreak.

You may have seen one of Lipkin’s many recent appearances in the media as an expert on Ebola. Yet he now says the future of his field lies not with acute infections, but in understanding the role microbes play in chronic diseases – one reason why ME/CFS has become a major focus his research.

Proving it

Once upon a time, proving a link between a pathogen and a disease was relatively straightforward. Usually it involved culturing a bug in the lab and showing the bug caused disease in animals too.

But for the most obviously infectious diseases like tuberculosis, smallpox or cholera, the responsible bugs have already been discovered. Lipkin and his team now hunt in more difficult territory, where linking disease with a microbial trigger is altogether more complicated.

We need to find out why people become ill, what sustains the illness and what we can do to mitigate it and prevent it.

Most microbes can’t be cultured in the lab, and often there isn’t an ‘animal model’ of the disease. How, asked Lipkin, would you create a mouse model for brain fog?

So the best way of demonstrating a microbe plays a key role in an illness such as ME/CFS is to show you can treat patients with drugs that target that microbe and that the patients improve or recover – or to find a vaccine that can prevent the illness. No doubt this is just the kind of proof that patients would most appreciate.

[After outlining Lipkin’s work in tracking down the cause of a number of chronic illnesses his talk returned to ME/CFS:]

On the trail of ME/CFS

In a series of illnesses Lipkin has shown how he follows the evidence wherever it leads. And now he has a plan for ME/CFS.

Given his background, the research almost inevitably started with a pathogen hunt, but so far they have drawn a blank.

They used a technique he’d developed called Mass Tag PCR to search for specific pathogens in blood plasma (including enteroviruses, influenza A virus, herpes virus and Borrelia bacteria), but they found no significant differences between patients and controls.

Then, working with Dr. Jose Montoya, Lipkin moved on to high-throughput sequencing that can detect any pathogen, but again they found no specific microbes linked to ME/CFS. They did find that a large but poorly-understood group of viruses – anelloviruses – were less common in patients than controls, but the significance of this is unclear.

The next step is to look in white blood cells (as opposed to plasma), where viruses such as herpes might be hiding out.

Lipkin explained they had profiled cytokines in ME/CFS patients, as had several other groups, but the unpublished results can’t be shared here.

Metabalomics: chemical clues in the blood

Lipkin, like many other researchers, believes the emerging field of metabolomics has the potential to reveal a great deal about diseases. Metabolomics is the study of the complete set of ‘metabolites’, all the small chemicals in any tissue or the blood that result from metabolic processes, such as amino acids or hormones. Diseases may have particular chemical fingerprints that will give clues about what’s gone wrong in the body, which is why Lipkin is keen to develop his work on this in ME/CFS.

He pointed out that the blood metabolome includes many molecules made by the gut microbiome, as a lot of small molecules cross the gut wall to the blood. For example, some gut bacteria can convert a chemical found in beans and fish into tryptophan, which is actively transported across the gut into the blood. The body needs tryptophan to make the neurotransmitter serotonin.

The gastrointestinal microbiome’s potential to send chemicals into the body is a big reason Lipkin wants to focus on it: “I think it produces compounds which traffic through the body or into the brain and cause all sorts of curious diseases”. He added that infection can lead to changes in the microbiome, which could influence the illness. And the microbiome also has the capacity to turn on and turn off the immune system. So the microbiome could be playing a role in ME/CFS in several different ways.

Lipkin is crowdfunding for his microbiome work after twice being turned down by the NIH for strange reasons (reviewers of his application said the illness was either psychosomatic or down to a herpes virus infection in white blood cells).

Lipkin wrapped up by outlining the key ways in which he’s trying to understand ME/CFS. As well as the microbiome and metabolomic work, and cytokine studies in press, he’s planning:

• Further pathogens searches, this time in white blood cells (where herpes viruses, for instance, can hide out).
• Gene expression studies to see if patients have different genes active to healthy controls, which could help show what’s going wrong
• Proteomics, which is the ‘protein fingerprint’ of the blood much like metabolomics is the chemical fingerprint. Again, differences between patients and controls might reveal clues about what’s going wrong in the illness.
• Functional Immunology with the National Institute of Allergies and Infectious Diseases.

Add these to the completed cytokine study and earlier pathogen hunts and you have a comprehensive programme of research into the possible causes of ME/CFS.

Almost the last thing that Lipkin said in the whole talk really made me sit up as it might explain why he’s investing so much energy in ME/CFS. While Lipkin made his name working on acute infections like SARS and Ebola, he now feels the action is moving to chronic illness:

‘I think that the future of microbiology and immunology really rests with understanding microbes and immune responses to microbes and toxicology in chronic diseases … recently a large focus of our research has been ME/CFS.’

Read more about Dr Lipkin’s talk:

Hunting down the cause of ME/CFS & other challenging disorders – Lipkin in London