Some history of hype regarding the human genome project and genomics

Just taking some notes here – relates to a discussion going on online.  Would love pointers to other references relating to hype and the human genome project (including references that think it was not overhyped).  I note – see some of my previous posts about this issue including: Human genome project oversold? sure but lets not undersell basic science and various Overselling Genomics awards. 

Here are some things I have found:

White House press conference on announcing completetion of the human genome

Genome science will have a real impact on all our lives — and even more, on the lives of our children. It will revolutionize the diagnosis, prevention and treatment of most, if not all, human diseases. In coming years, doctors increasingly will be able to cure diseases like Alzheimer’s, Parkinson’s, diabetes and cancer by attacking their genetic roots. In fact, it is now conceivable that our children’s children will know the term cancer only as a constellation of stars.

Collins et al. New Goals for the U.S. Human Genome Project: 1998–2003

The Human Genome Project (HGP) is fulfilling its promise as the single most important project in biology and the biomedical sciences— one that will permanently change biology and medicine.

Human Genome -The Biggest Sellout in Human History

The Human Genome Project: Hype meets reality

NOVA: Nature vs. Nurture Revisited

After a decade of hype surrounding the Human Genome Project, punctuated at regular intervals by gaudy headlines proclaiming the discovery of genes for killer diseases and complex traits, this unexpected result led some journalists to a stunning conclusion. The seesaw struggle between our genes (nature) and the environment (nurture) had swung sharply in favor of nurture.

The human genome project, 10 years in: Did they oversell the revolution? in the Globa and Mail by Paul Taylor referring to: “Deflating the Genomic Bubble

Also see Genomic Medicine: Too Great Expectations? by PP O Rourke

Also Has the Genomic Revolution Failed?

And Human genome 10th anniversary. Waiting for the revolution.

Science communication in transition: genomics hype, public engagement, education and commercialization pressures.

The Medical Revolution in Slate.

A Decade Later, Genetic Map Yields Few New Cures in the New York Times.

In announcing on June 26, 2000, that the first draft of the human genome had been achieved, Mr. Clinton said it would “revolutionize the diagnosis, prevention and treatment of most, if not all, human diseases.” 

At a news conference, Francis Collins, then the director of the genome agency at the National Institutes of Health, said that genetic diagnosis of diseases would be accomplished in 10 years and that treatments would start to roll out perhaps five years after that.

NNB report: Ten years later, Harvard assesses the genome map where regarding Eric Lander:

At the same time, , he said genomic research has “gone so much faster than I would have imagined.” He cited ” an explosion of work that will culminate, I think in the next five years, in a pretty comprehensive list of all the target that lead to different kinds of cancers and give us a kind of roadmap for finding the Achilles heel of cancers for therapeutics and diagnostics.”

while at the same time he blamed the press for the hype

From Great 15-Year Project To Decipher Genes Stirs Opposition in the Times June 1990

‘Our project is something that we can do now, and it’s something that we should do now,” said Dr. James D. Watson, a Nobel laureate who heads the National Center for Human Genome Research at the National Institutes of Health. ”It’s essentially immoral not to get it done as fast as possible.”

  • Note the article has many complaining about the hype in the genome project even then ..

From SCIENTIST AT WORK: Francis S. Collins; Unlocking the Secrets of the Genome

And, Dr. Collins adds, there is nothing more important in science and medicine than the project he heads

Dr. Collins predicts that within 10 years everyone will have the opportunity to find out his or her own genetic risks, to know if cancer or heart attacks or diabetes or Alzheimer’s disease, for example, lies in the future. 

From READING THE BOOK OF LIFE: THE DOCTOR’S WORLD; Genomic Chief Has High Hopes, and Great Fears, for Genetic Testing June 2000 in the NY Times

The story goes through some predictions Francis Collins made for the future in a talk.  These included:

  • BY 2010, the genome will help identify people at highest risk of particular diseases, so monitoring efforts can focus on them.
  • In cancer, genetic tests will identify those at highest risk for lung cancer from smoking. Genetic tests for colon cancer will narrow colonoscopy screening to people who need it most. A genetic test for prostate cancer could lead to more precise use of the prostate specific antigen, or P.S.A., test by identifying those men in whom the cancer is most likely to progress fastest. Additional genetic tests would guide treatment of breast and ovarian cancer.
  • Three or four genetic tests will help predict an individual’s risk for developing coronary artery disease, thus helping to determine when to start drugs and other measures to reduce need for bypass operations.
  • Tests predicting a high risk for diabetes should help encourage susceptible individuals to exercise and control their weight. Those at higher risk might start taking drugs before they develop symptoms.
  • BY 2020, doctors will rely on individual genetic variations in prescribing new and old drugs and choosing the dose. Pharmaceutical companies will take a second look at some drugs that were never marketed, or were taken off the market, because some people who took them suffered adverse reactions. It will take many years to develop such drugs and tests.
  • Cancer doctors will use drugs that precisely target a tumor’s molecular fingerprint. One such gene-based designer drug, Herceptin, is already marketed for treating advanced breast cancer.
  • The genome project holds promise for the mental health field. ”One of the greatest benefits of genomic medicine will be to unravel some biological contributions to major mental illnesses like schizophrenia and manic depressive disease” and produce new therapies, Dr. Collins said.

Overselling genomics award #7: Ron Davis & Forbes for PR presented as "essay"

Wow.  Just saw this tweet by Dan Vorhaus:

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So I decided to check it out. The piece is titled It’s Time to Bet on Genomics and it is, well, just completely in appropriate.  Sure – it does take on an article that itself was over the top in downplaying the power of genomics (see Erika Check Hayden’s article about that issue here).  But then Davis goes on to write about a company founded by an ex post doc of his for which Davis is one of the advisors (he does kindly let us know this, but still …).  And what he writes he is a big big pile of fluff with no evidence presented.  Among the lines in the “essay” I find disturbing:

  • One of the most interesting of these is being developed by Genophen
  • Genophen’s application is rather breathtaking in its ambition.
  • Genophen’s “risk engine”—a simple term for some very complex data mining and computer modeling—will map your risk factors against the world’s vast library of medical research and then offer up a personalized set of behavior and treatment recommendations that can help you reduce those risks . . .  and even prevent disease itself.
  • We are now at the point where genomics-enabled medical technology can run various what-if scenarios and show you whether diet, exercise, medication, or some other factor or combination of factors has the greatest statistical likelihood of reducing that risk. The information can then be visually displayed through charts and graphs and made available to patients and their doctors via secure web-based portals.
  • But instinctively I believe it to be true, and anecdotally Genophen’s first trial provided some confirmation.
  • “The trial changed my life,” one female participant who wishes to remain anonymous told me.

All of this without any link to a paper, without any data, without any real details.  Shameful.  Not saying genomic medicine does not have a lot of promise.  But this “essay” is so excessively focused on PR for one company that there is no reason to have any faith in anything said in it.  I am therefore giving Ron Davis and Forbes my coveted Overselling Genomics Award (#7).  Plus I think Forbes deserves some sort of award for “Publishing PR” but I will have to think one of those up.  This piece almost certainly never should have been published at Forbes.Com without many many more caveats.  Yuck.

UPDATE – here is a screenshot from the Forbes Web site.  It is marked as “Forbes Leadership Forum” … hard to tell whether it is meant as an essay, editorial, op-ed, or what.

Human genome project oversold? sure but lets not undersell basic science

Well, the piling on the human genome project continues, it seems at an accelerating pace.  I think most of this comes from the fact that we are in the range of the 10 year anniversary right now.   Here are some examples of recent stories suggesting the human genome project (or projects, if you count the public effort and Craig Venter’s effort as separate) have had little benefit:

  • 7/31/10: The Human Genome Project: 10 Years Later, Progress but Still a Puzzle – WNYC. Interesting piece by Sarah Kate Kramer discussing the limited clinical value of the HGP.  Includes some criticisms of personalized genomic medicine. 
  • 7/29/10: Spiegel interview with Craig Venter with the headline “We have learned nothing from the genome”.  Has lots of interesting tidbits.  Love the Venter line “Well, nobody likes to be beaten — by superior intelligence, planning and technology. That gets people upset.”  But I note Craig emphasizes the basic science value of human genome data.
  • 7/6/10: Public Radio mini story about Mike Mandel’s article on the failure of the human genome project.
  • 6/12/10: Nick Wade’s NY Times article on “A decade later, genetic map yields few new cures“.  In this Wade discusses many of the issues with both the sequencing of the human genome and some of the spinoff projects (and also butchers some evolutionary biology for which I gave him a twisted tree of life award). 
These are but a small sampling of the many many blogs, articles, and other reports that either directly state or suggest that much of the money spent on the human genome project was a waste.

Certainly, contrary to the suggestion of some of these articles, there have been some practical benefits that have come directly or indirectly from human genome sequencing.  But equally certainly, these critiques have a segment of truth to them in that the practical benefits have been few and far between.

Normally, one would not expect too many direct practical benefit to come from this kind of science project.  But alas, the problem here is that many of the key players (e.g., Eric Lander, Francis Collins, Craig Venter) in the sequencing of the human genome(s) oversold the potential benefits that could come from the sequencing.  In a way, it was their job to oversell the sequencing, since each was a cheerleader in ways for getting others to do a lot of work.

Many people knew at the time that this overselling was going on.  It was talked about extensively at various genome conferences and even occasionally in the press and scientific literature (boy do I wish I had had a blog then, because I was one of those people at conferences practically begging people to not oversell the benefits of the project – I now even give out an “overselling genomics award” on my blog ).  The cautionary voices were mainly saying that there was no need to oversell the project and that we should stick to the benefits of “knowing” ourselves and not guess about how it will lead to immediate cures for diseases.  And many said “If you oversell this now, it will come back to bite you

And thus it is not surprising to me that there is somewhat of a backlash now.  But there is a very dark side to the backlash that has potential to hurt science for many years to come.  If there is a need in the future for large scale science / medical projects, I can guarantee that some critics will step up and say things like “Well the war on cancer failed.  And the human genome project failed.  Why should we trust you now?

The problem here is that the human genome project should never have been sold as a means to a series of practical ends.  It should have been sold as a massive basic science project, much like going to the moon or building a giant linear accelerator.  That is, the human genome project was, and still really is, about knowledge.  It is about knowing ourselves.  It has enormous potential benefits in all sorts of areas, like human medicine.  It should greatly aid and abet studies of human biology and genetics and disease.  But given that benefits that come from such studies are impossible to predict, the human genome project should have been presented in a different way.  We need to discuss more in public why basic science is important even if one cannot predict what the benefits are.

In many ways, this is very much like the “war on cancer” which some have argued failed because we still have cancer killing a lot of people.  But this is off base because in fact the war on cancer has provided us with an incredible baseline of information about the biology of cancer.  We need to do a better job in all of these cases of defending the need for knowledge, and discussing how fighting cancer and curing diseases is not the same as building a big bridge or road.

The best person discussing this issue for the last ten or so years in my opinion has been Harold Varmus, who was once the head of NIH and is now the new director of the National Cancer Institute.  I have heard him repeatedly defending the “war on cancer” in terms of its basic science benefits.  For example see his comments on Science Friday 1/30/2009 and 7/16/2010.  There just have not been too many people doing a good job of this with genomics.  Venter and Collins have been OK here and there.  But we need more.

On a related note, we probably should have more discussion about how the money spent on the genome project and the war on cancer pales in comparison to money we spend on other things (e.g., interest on the national dept, wars, etc) but perhaps that is a side discussion.

Most importantly, we need to bring out to the public more of a discussion of the benefits from basic science. Here are some useful resources if you want to try and help:

I also encourage people to look at the National Academy of Sciences report A New Biology for the 21st Century: Ensuring the United States Leads the Coming Biology Revolution.  I note, I was one of the coauthors.  You can download the PDF of the whole document after giving your email address.
I am going to start a new series here on this blog called “Benefits of basic science” where I will be discussing these issues.  I encourage others out there to also bring more to the forefront discussions of the need for basic science.

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UPDATE

Also see

Overselling genomics award #6: Quake/Helicos & the "democratization" of sequencing

For those interested in so-called “third generation” DNA sequencing systems, this week has had some buzz with the release of a publication in Nature Biotechnology reporting the sequencing and analysis of a human genome using a Helicos Heliscope sequencer. In this paper Stephen Quake and colleagues generated short read sequences from Quake’s DNA using this machine and then analyzed them by comparing them to reference human genomes.

Certainly, what they did was cool. And the use of the Helicos equipment is a good thing for that company and it’s development of single molecule sequencing. And given the “race” if you want to call it that for the $1000 genome, it is thus not surprising that this paper received a lot of coverage from all sorts of angles because they claim it involved the cheapest sequencing of a human genome yet achieved.

So first I want to commend Quake and Helicos for an important step in third generation sequencing. Quake mind you is one guy who is constantly inventing cool new techniques of great use in genomics and biology and he is always worth checking out.

But in this case, there are some aspects of what they claim they achieved here that are very off putting. In particular, I am concerned with the supposed “democratization of sequencing” that they think this project embodies (e.g., see some of the quotes in this). The basis for their concluding that democratization has happened here is that they believe this sequencing (of Quake’s genome) was done at lower cost and with less effort than previous human genome sequencing efforts. To back this up they make a table (Supplemental Table 1) detailing estimates of these values for 8 human genome papers (the original Lander et al and Venter et al ones, as well as Watson’s genome, etc) that is meant to represent some of this information).

In essence Quake et al are doing the following math (my formula, not theirs, but their discussions imply basically this)

D = B/(E*C)
Democratization factor (D) = # of bases sequenced (B) / (amount of effort (E) * cost (C))

That is, with more sequence, less effort, or less cost, the more democratized sequencing is. Sounds fine in some ways. Except when you look at the details.

For example consider the cost (C) of the sequencing. They report that the cost for the sequencing was < $50,000. But this number is misleading since, for example, they do not include any aspect of the cost of actually buying and setting up the machine. For more detail on the flaws in the cost calculation and for more detail on the whole story see Times Online and Dan Macarthur at Genetic Future and GenomeWeb).

However, more disconcerting to me is what they do with the rest of the implied calculation.

For example, they treat all the projects in essence as though they are equal in terms of total number of bases sequenced (B) because I guess after all, all were sequencing human genomes. But this is not fair since the depth of sequencing and the quality of sequencing varies between the projects and more recent projects, such as theirs, make use of the data from prior projects, which allows them to gather less data (e.g., in their paper here they assemble the genome by tiling the reads against reference genomes, thus allowing them to do lower coverage than would be required for denovo assemblies of genomes).

But even worse – the way they calculate effort required (E) is flabbergasting.

They seem to infer this in two ways. First, they make use of the number of runs of the machine that are required. They apparently used four runs while they claim that the use of second generation sequencing methods required many more runs. And many have been questioning this claim (e.g., see Chad Nusbaum’s quotes in the GenomeWeb article).

It is the second way that they infer effort that is perhaps the most annoying. They infer this from number of authors on the papers describing the sequencing of these human genomes (e.g., In Supplemental Table 1 they say “number of authors” is “an estimate of labor.”) And the big thing for Quake et al is that there are only three authors on their paper and dozens to hundreds on other human genome papers. Based on this lower number of authors they conclude that their work required less effort and discuss this as evidence for further democratization of sequencing.

Now suppose we gloss over that there is no way to infer amount of effort by number of authors (e.g., letters to the editor, which usually do not require a lot of effort, can sometimes have hundreds of authors while Origin of Species had but one author and was, shall we say, a lot of work). Even worse to me is that they are trying to compare their paper which is focused almost entirely on the technical aspects of the sequencing with other papers that spend much more effort on studying and discussing what the genomes might mean. For example the Venter/Celera and the public human genome papers are complex detailed volumes with analysis of everything you could think of. To compare the effort required to do this with the effort required to do what they did in the Quake paper which was pretty much assembly and analysis of SNPs is inappropriate and actually offensive.

Given the number of areas that they have oversold how their project has reduced effort and cost for sequencing a human genome and how this implies democratization, I am giving Quake and Helicos my coveted “Overselling genomics award“. Again, not that what they did was not cool or interesting, but by overselling it, it detracts from everything they achieved.

Overselling genomics Award #5: Duckweed will save the world

OK. I really wanted to leave this one alone because it involves the Joint Genome Institute (JGI) where I work part of the time. And I really like JGI and what it is doing in many aspects of genomics. But this one is just so over the top that I could not leave it alone. There is a press release from Rutgers that came out regarding a new project to sequence the duckweed genome (see News: Duckweed genome sequencing has global implications) and the Eureka release here

And this one is just so over the top in terms of overselling I do not know where to begin. First, they had me at the title

Duckweed genome sequencing has global implications

But the subtitle is even better

Pond scum can undo pollution, fight global warming and alleviate world hunger

There is really little else to say. I commend the JGI and DOE for supporting this work as it sounds reasonable and work on this organism may have many uses. But, umm, this was the most obvious “Overselling genomics award” I have ever given.

Overselling genomics award #4: University of Western Ontario and Graham Thompson on honeybee altruism

In my blog I give out some snarky awards for things that annoy me including the Genomics by Press Release Award and the Adaptationomics Award and the Overselling Genomics Award. Sometimes I really want to give something an award but I am not sure what it should get. That is the case here. There is what I find to be a painful press release on “Selfish Genes” in honeybees put out by University of Western Ontario. This press release relates to a paper being published in Genetics. on QTL mapping in honeybees and searching for alleles/genes that suppress the reproductive activity in worker bees. This suppression is a form of altruistic behavior in a way and has been the subject of a good deal of research. Basically, the ended up mapping some of the suppression to a few regions of the genome.

The press release however, goes way way overboard in interpreting their results and claiming “New Discovery Proves ‘Selfish Gene’ Exists.” They imply throughout the press release that prior work simply suggested that selfish genes were theoretically possible in this case and that now with their results they have been proven. For example they quote the lead author Graham Thompson:

This means that the ‘selfish’ gene does exist, not just in theory but in reality.

This is way beyond an overstatement. Their results are nice and interesting but they are part of a continuum of work on bees (and other selfish systems) and do not in any obvious way suddenly prove the existence of this selfish gene compared to prior work that they imply was just guesswork. I am personally baffled by the extent of this claim — basically ignoring work by many others as well as work in a variety of systems outside of bees. They end the press release with the following:

“This basically provides a validation for a huge body of socio-biology,” says Thompson, who adds the completion of Honey Bee Genome Project in 2006 was crucial to this discovery.

For that last statement, I am thus giving them my “Overselling genomics award” #4. But they easily could have gotten a few others.  

NOTE – I had changed the award to just U. Western Ontario and not including Thompson because it is the University that appears to be responsible for the press release not Thompson.  However, a commenter (Oliver) convinced me that if we want to clean up press releases we need to make the scientists involved in the story help make sure the press releases are clean, so I put Thompson back in.

Hat tip to T. Ryan Gregory for pointing this out. And you should check out his new Genomics by press release “award” at his blog Genomicron. I will probably be writing about the same story soon.

Overselling genomics (and men) award #3 – Newsweek Magazine

Newsweek Magazine has a feature on the “10 hottest nerds” that they say are “10 of the most esteemed biologists” in the w0rld. And they ask for their insights into various things. The people are

  • Eric Lander
  • Leroy Hood
  • Craig Venter
  • David Botstein
  • Svante Paabo
  • Philip Sharp
  • Rudolph Jaenisch
  • Kari Stefansson
  • George Church
  • Jay Keasling

Sure these people have done good things and I truly respect most of them in many ways. But are they kidding me? This is who they pick? First of all, all men? Mostly, all people who have been around the block too. Plus, almost all these people work in something connected to genomics (Lander, Hood, Venter, Botstein, Paabo, and Church are major genomics players; Keasling and Sharp and Stefansson are heavily genomics-based).

They couldn’t come up with a single woman? Or anyone doing anything else? Or any new researchers? This whole thing is completely egregious. There are plenty of completely cool things going on in biology that have little if any connection to genomics, that are not men, and/or are not established researchers.

And to get the conversation going here are some people they could have considered to diversify in at least one dimension (i.e., the male versus female thing):

I came up with this list in about 20 minutes, based mostly on people I know. And of course, there are TONS of other women in biology who are doing fantabulous research. Even if one did not know anything, a little time on Google pulls up a vast collection of resources — (e.g., see L’Oreal’s for Women in Science page or this Wikipedia page for more suggestions). And of course lets not forget that genomics is not the only thing going on in biology.

So – Newsweek – you are getting my third “Overselling Genomics Award” and on top of that a bonus “Overselling Men” award. All I can say is – what were you thinking?

Overselling Genomics Award #2

Well, all I can say is “Aaaaargh” again. So I am awarding my second overselling genomics award to a Press Release from U. Florida entitled Conquest of land began in shark genome” relating to a paper in PLoS One on shark development . The press release centers on a reported finding that

Using molecular markers to study the formation of skeletal cartilage in embryos of the spotted catshark, UF scientists isolated and tracked the activity of Hox genes, a group of genes that control how and where body parts develop in all animals, including people.

Now admittedly, this is not genomics here – but the press release just had to use genomics in the title so my automated google search for “genome” and “evolution” picked it up. So – why do they get the overselling award? Read more in the press release:

The finding shows what was thought to be a relatively recent evolutionary innovation existed eons earlier than previously believed, shedding light on how life on Earth developed and potentially providing insight for scientists seeking ways to cure human birth defects, which affect about 150,000 infants annually in the United States.

Yes that is right, this genome-ish gene expression study in sharks is going to help cure human birth defects (note the paper in PLoS One seems entirely reasonable … this is another case of press releases being disconnected from the science – and is another reason to support OA publications because here you can actually all go and read the paper and ignore the press release).

In addition, the press release says

“We’ve uncovered a surprising degree of genetic complexity in place at an early point in the evolution of appendages,” said developmental biologist Martin Cohn, Ph.D., an associate professor with the UF departments of zoology and anatomy and cell biology and a member of the UF Genetics Institute. “Genetic processes were not simple in early aquatic vertebrates only to become more complex as the animals adapted to terrestrial living. They were complex from the outset. Some major evolutionary innovations, like digits at the end of limbs, may have been achieved by prolonging the activity of a genetic program that existed in a common ancestor of sharks and bony fishes.”

Now I accept that the specific details of Hox gene expression here might have been surprising but what friggin evolution textbook are these people reading if they are surprised that there is not a chain of life going from less complex to the pinnacle of complexity in humans? Hopefully not mine.

Overselling genomics awards

Genomics is great. It really is. But is has also been absurdly oversold by many, starting with those who implied sequencing the human genome would cure all diseases. So I have decided to start a new line of this blog – the “Overselling genomics awards”

My first award goes to the Stuart Truelson for a Commentary for the California Farm Bureau Federation. The essay has some OK points about genomics but is a bit overzealous about the benefits that come from genomics. The essay ends with:

The genomics age is here, whether some like it or not. And, any effort to impede potential benefits that genomics offers humankind–from more and better food to breakthroughs in health and life-saving medicine–should raise moral and ethical questions that are even more serious than those surrounding the science itself.

Sounds a bit like those who say “Any discussion of the war makes you unpatriotic.” And thus Mr. Truelson gets my first award, not just for overselling genomics, but for being so icky about it.