Thursday, 3 April 2014

How useful is genomics for drug discovery?

In a previous post, I discussed a number of large sequencing projects, including by the governments of Saudi Arabia and the United Kingdom, which are sequencing the genomes of 100,000 of their citizens each.

I also lamented that these projects are exclusively government-funded, and that big pharma and biotechnology companies don't appear to consider large-scale sequencing a viable approach to drug discovery. Well, actually some of them do.

Three recent developments stand out: 

Regeneron, a large biopharmarmaceutical company, has teamed up with Geisinger Health Systems, a local American healthcare network, to sequence 100,000 exomes at an estimated cost of $100 million. Geisinger has detailed electronic health records of its patients, which will help with the interpretation of the data.

Amgen, another large biopharma company, announced that it would partner with the Broad Institute, one of the world's biggest genomics research institutes, to discover new drug targets. Prior to that, Amgen had acquired DeCode Genetics, which despite producing first-class science had been struggling.

And finally, the pharmaceutical giant GSK, together with two European genomics research centres, the EBI and the Sanger Institute (where I'm based), launched the Centre for Therapeutic Target Validation (CTTV), which will validate drug targets using a genomic approach.

Overall, it seems that pharmaceutical and biotech companies indeed have an increasing appetite for applying genomics to drug discovery. The question remains how successful this approach will be, and how much of an advantage it confers to the companies that invest in it.

Sunday, 9 March 2014

Why so many huge sequencing projects?

In the United Kingdom, a project to sequence 100,000 whole genomes is under way. Saudi Arabia has started another 100,000 genome sequencing project. And a few days ago, bioentrepreneur Craig Venter announced a new company called Human Longevity, which is going to initially sequence 40,000 genomes, followed by hundreds of thousands later. Most likely, additional projects on a similar scale will be kicked off over the next months and years.

All this sequencing is not going to be cheap. For example, the British government has put aside £100 million (around $170 million) for its project. How can these costs be justified to taxpayers and investors?

One reason for government-funded projects like the one in Saudi Arabia and the UK is that they are going to directly benefit the sequenced patients. The other and probably more significant reason is that the resulting data will impact the development of new cures.

Genetic variants protecting against common diseases such as Alzheimer's and diabetes have already been discovered. Any drug that mimics the effect of those variants would be likely to also protect against the disease whilst at the same time being safe. The caveat is that rare protective variants can only be detected by studies involving tens or hundreds of thousands of people. Hence the need for sequencing-megaprojects.

Given the potential impact on drug discovery, it may seem puzzling that the initiative comes from governments and startups, rather than from established pharmaceutical companies, whose core competency is, after all, drug discovery.This is probably due to both the relatively conservative nature of most pharmaceutical companies, as well as the so far unproven nature of the approach.

Sunday, 26 January 2014

How happy are 23andMe customers?

In October last year, I joined several of my colleagues at the Sanger Institute to order a bunch of direct-to-consumer genetic testing kits from 23andMe. The reason for the batch order was the associated discount. The total cost per person turned out to be around $130, of which $80 were for the kit and $50 for shipping from California to England.

Most of us received our data earlier this month, and I thought that it could be interesting to learn what my colleagues, all of whom probably know more about genetics than the average person, thought of their experience. This is why I asked them to fill in a small survey. Here are the results.

Results of a survey of 16 23andMe users at the the Wellcome Trust Sanger Institute. Click on the figure to enlarge it.

The results are largely self-explanatory. In the following, I am elaborating on a few points that may not be obvious.

Everyone thought that the test was worth what they had paid for it, and 7 out of 16 changed their diet, exercise or lifestyle habits as a result. Respondents generally thought that 23andMe did a good job in presenting the data.

We ordered in October 2013, before the FDA told 23andMe to stop providing health-related results, which meant that we were able to get ours. There are dozens, if not hundreds, of diseases the test returned information on. For the most severe ones, such as Alzheimer's, users had to click through a series of questions affirming that they really want to see their results. This is due to the potentially severe impact of these variants. For example, those who have two copies of a specific APOE gene variant are around ten times more likely develop Alzheimer's. 13 out of 16 respondents chose to see their data on these potentially high-impact variants.

Generally, people thought the health section of their test was interesting. The same cannot be said about the ancestry section, which provides information about genetic origins of the user's family. This result is likely to cause concern for 23andMe, as they have been asked by the FDA to stop providing health information and as a result are now concentrating on ancestry information. A majority (11 out of 16) users thought that 23andMe should not be regulated by regulatory authorities like the FDA.

Do you have any thoughts on the survey or on 23andMe? Please feel free to share them below.

Sunday, 19 January 2014

Do you still care what I've been reading?

As promised, here are the tweet-summaries of the non-fiction books I've been reading last year, in no particular order:

The Body Economic: Why Austerity Kills
Slashing healthcare budgets decreases the quality of healthcare. You don't say (The Body Economic, by David Stuckler and Sanjay Basu)

The Genius of Dogs - Discovering the Unique Intelligence of Man's Best Friend 
You think your dog understands you? Not a coincidence: That's what it was bred for (The Genius of Dogs, by Brian Hare and Vanessa Woods)

If Dogs Could Talk: Exploring the Canine Mind
Wolves have scent glands on the balls of their feet (If Dogs Could Talk, by Vilmos Csányi)

The Mystery of Capital: Why Capitalism Triumphs in the West and Fails Everywhere Else 
If you want  people to get rich (i.e. own lots of property), you need good property rights (The Mystery of Capital, by Hernando de Soto)

The World Until Yesterday
Traditional societies got some things figured out that we in West still struggle with (The World until Yesterday, by Jared Diamond)

Why America Is Not a New Rome 
Both America and the Roman Empire are less powerful than most people assume (Why America is Not a New Rome, by Vaclav Smil)

The Sleepwalkers: How Europe Went to War in 1914 
Not predictable: Lots and lots of things had to go wrong for World War I to happen (The Sleepwalkers, by Christopher Clark)

Rapt: Attention and the Focused Life
Being good at something means paying attention to the right things. Recommended. (Rapt, by Winifred Gallagher)

Drugs 2.0: The Web Revolution That's Changing How the World Gets High. 
It's easy to buy drugs off the internet, and there isn't much anyone can do about it (Drugs 2.0, by Mike Power)

German Genius
German history is one bloody musician, philosopher and scientist after another (The German Genius, by Peter Watson)

The Knack: How Street-Smart Entrepreneurs Learn to Handle Whatever Comes Up 
How streetsmart entrepreneurs write a business book that makes no sense (The Knack, by Norm Brodsky and Bo Burlingham)

So Good They Can't Ignore You: Why Skills Trump Passion in the Quest for Work You Love 
The way to find the perfect job is not to not settle and keep looking, but to become good at what you do (So Good They Can't Ignore You, by Cal Newport)

Them: Adventures with Extremists
White supremacists, Muslim extremists and conspiracy nuts can be nice when meeting them in person (Them, by Jon Ronson)

1913 - Der Sommer des Jahrhunderts 
Vor 101 Jahren war die Welt nicht so anders (1913, von Florian Illies)

Abundance: The Future Is Better Than You Think 
We probably shouldn't worry too much about running out of natural resources (Abundance, by Peter Diamandis and Steven Kotler)

Nonzero: The Logic of Human Destiny
 Maybe history is not so much the product of divinity as the realization of divinity (Nonzero, by Robert Wright)

L'histoire du type qui cherche une aiguille dans une botte de foin et qui trouve la fille du fermier (Fabuleux Hasards, de Claude Bohuon et Claude Monneret)

Presentation Zen: Simple Ideas on Presentation Design and Delivery
When presenting, don't expect people listen to you and read your slides at the same time (Presentation Zen, by Garr Reynolds)

Monday, 13 January 2014

Do you care what I have been reading?

If you don't - and I wouldn't blame you - ignore this post.

Over the next few days, I'll summarise the non-fiction books I've read in 2013 in Twitter format, using the hashtag #condensedBooks. Until then, here is a list of the books I read and tweeted about the previous year (i.e. in 2012):

The Checklist Manifesto: How to Get Things Right
Why you'd want your surgeon to operate on you by checklist. Best book I read in 2012 (The Checklist Manifesto, by Atual Gawande)

Moonwalking with Einstein: The Art and Science of Remembering Everything
Being able to remember 10,000 random numbers doesn't mean you'll remember where you left your keys (Moonwalking with Einstein, by Joshua Foer)

Chess grandmasters aren't particularly smart. They've just practised a lot (Bounce, by Matthew Syed)

The Psychopath Test: A Journey Through the Madness Industry
Psychopaths can be fun, too (The Psychopath Test, by Jon Ronson)

The Golden Spruce: A True Story of Myth, Madness and Greed
This book confirms what I always knew: Lumberjacks are the pinnacle of manliness (The Golden Spruce, by John Vaillant)

Better: A Surgeon's Notes on Performance
Improvement is a question of character (Better, by Atul Gawande) 

Priceless: The Myth of Fair Value (and How to Take Advantage of It)
Cheap things don't sell (Priceless, by William Poundstone)

The Creative Destruction of Medicine: How the Digital Revolution Will Create Better Health Care
Personalised medicine is more than just genomics (The Creative Destruction of Medicine, by Eric Topol)

The Moral Landscape: How Science Can Determine Human Values
Just because people don't agree on what's moral doesn't mean that there is no right answer (The Moral Landscape, by Sam Harris)

Who: The A Method for Hiring
It's really, really hard to hire the right people. Checklists help (Who, by Geoff Smart and Randy Street)

Soccernomics: Why England Loses, Why Germany and Brazil Win, and Why the U.S., Japan, Australia, Turkey--and Even Iraq--Are Destined to Become the Kings of the World's Most Popular Sport
Football clubs should spend more on signing data crunchers and less on aging celebrity footballers (Socceronomics, by Simon Kuper and Stefan Szymanski) 

The Lean Startup: How Today's Entrepreneurs Use Continuous Innovation to Create Radically Successful Businesses
The central mission of a startup should be to learn what to do, not how to do it (The Lean Startup, by Eric Ries)

Kingpin: How One Hacker Took Over the Billion-Dollar Cybercrime Underground
Credit card fraud has a certain nerdy glamour to it (Kingpin, by Kevin Poulsen)

The Genome Generation
Agrigenomics is at least as exciting as other sub-disciplines of genomics (The Genome Generation, by Elizabeth Finkel)

Drive: The Surprising Truth About What Motivates Us
Don't rely on common sense when trying to motivate people. They are too complex for that (Drive, by Daniel Pink)

How We Decide
The hardest problem is to know when to stop thinking and trust your instincts instead (How We Decide, by Jonah Lehrer. This book has been retracted by its publisher since I read it)

The Power of Habit: Why We Do What We Do, and How to Change
Will power rules: "Self-discipline has a bigger effect on academic performance than does intellectual talent" (The Power of Habit, by Charles Duhigg)

Thursday, 19 December 2013

How is non-invasive prenatal testing getting on?

Almost two years ago, I wrote a series of posts on non-invasive prenatal testing (NIPT) of foetuses and the associated market. What has changed since?

In terms of technology, there hasn't been any big breakthrough. The principle behind NIPT has stayed the same: Some of the DNA in a pregnant woman's blood is of foetal origin. By sequencing that DNA, it is possible to reconstruct most of the genotype of the foetus, and to detect many severe genetic disorders from the 8th week of pregnancy onwards - earlier than with equivalent tests.

What has changed is the number of companies actually offering NIPT. At least seven companies worldwide currently sell NIPT, whilst several other are aiming for a 2014 market entry. The table below provides and overview.

Company (Test)
Conditions tested
Test price
Tests sold
Market entry
Ariosa (Harmony)
Trisomies 13, 18, 21, sex chromosome aneuploidies
150,000 until September 2013
May 2012
Beijing Berry Genomics (BambniTest)
Trisomies 13, 18, 21
Around $500

China, Worldwide
Trisomies 13, 18, 21

200,000 until October 2013

CellScape (Clarity)
In development

None yet

In development

None yet

LifeCodexx/ GATC (PraenaTest)
Trisomies 13, 16, 21
€1,150 ($1,580)
Year to August 2013: 6,000
August 2012
Natera (Panorama)
Trisomies 13, 18, 21, sex chromosome aneuploidies

December 2012
Sequenom (MaterniT21 Plus)
Trisomies 16, 21, 22, deletions causing various syndromes
$1,700 for uninsured patients
145,000 until September 2013
October 2011
Verinata/ Illumina (Verifi)
Trisomies 13, 18, 21, sex chromosome aneuploidies

March 2012

This list is incomplete in the sense that increasingly NIPT is also considered as an option by public health services. In the Netherlands, a NIPT trial will start in April 2014. In England, the National Health Service (NHS) is currently carrying out a study of NIPT called RAPID.

One aim of the NHS study is to compare the cost of NIPT to that of chorionic villus sampling (CVS). CVS is an invasive procedure that has traditionally been used for obtaining genetic material from the foetus. It involves taking a sample of the placenta and can lead to miscarriage. The advantage of CVS is that it gives relatively unambiguous results, whilst positive NIPT results still need to be confirmed by CVS or a similar procedure. Even so, the estimated total cost of using NIPT compared to CVS alone was 4% lower for one condition and 7% lower for the other condition. An important caveat of this estimate is that it only used NIPT for foetal sex determination in cases where this was disease relevant and not into detecting chromosomal abnormalities. 

The Dutch and English examples of public health service-provided NIPT points to a mistake that is easy to make when estimating the future market size for NIPT (and genetic diagnosis in general). A lot of health service providers may prefer to develop their own tests rather than rely on third party tests. This decreases the size of the market accessible to companies like Sequenom and Ariosa, especially in Europe.

Do you have any comments, or are there any NIPT companies or projects I haven't included? Please feel free to tell me in the comments section below.

Monday, 25 November 2013

Should 23andMe be regulated?

Today, the American Food and Drugs Administration (FDA) has sent a letter to 23andMe, the market leader in direct-to-consumer testing, asking them to immediately discontinue marketing their tests. Is it justified in doing so?

In my opinion, the answer is clearly yes.

That's although 23andMe has, I think, not marketed its services in any unethical way. Their website and their most recent TV ad avoid raising fears. This is in welcome contrast to many adverts by established pharmaceutical companies I see in the United States.

My point is that 23andMe's test should not be treated any differently than other diagnostic tests.

But is 23andMe a diagnostic test? On its website, the company lists the traits and diseases it returns information on. Whilst some of them, like ancestry or odour sensitivity, are harmless, others are specifically designed to inform on the risk for diseases including Alzheimer's, breast cancer, Parkinson's, and many more.

To claim that all 23andMe does is return information about variant-gene associations is disingenuous. By extension, there shouldn't be regulation of any diagnostic test, because all they do is return information on some marker-disease association. This may be a valid point of view, and if you hold it, you need to argue for the deregulation of the diagnostics market as a whole, and not just against the regulation of 23andMe.

A few weeks ago, I bought a test from 23andMe myself, but I haven't received the results yet. Does this make me a hypocrite? I don't think so.
Firstly, I strongly advocate that people have free access to their genetic information, and to their medical data in general. That does not mean that the quality of disease-relevant genetic tests should not have to meet the same requirements than other diagnostic tests.
Secondly, I feel that because I am working in the field, I have a good grasp of how reliable genotyping data as that provided by 23andMe is and what it can tell me. If my test returned anything that was of serious concern to me, I wouldn't dream of taking drastic action without further testing to confirm the results. I believe that this distinguishes me from some other people, including the least educated and vulnerable ones.

Some people may feel that the FDA has an anti-genomics agenda. I don't know whether that's true, but I don't see the letter it sent to 23andMe as any evidence for it. If genetic testing that fulfils regulatory requirements for $99 is not possible, that's unfortunate, but why should an exception be made in this case?

The opinions I express on this blog are not necessarily those of my employers or my funding body.