James Watson Says Antioxidants May Actually Be Causing Cancer

Illustration for article titled James Watson Says Antioxidants May Actually Be Causing Cancer

Celebrated geneticist James Watson, one of several researchers who won the Nobel Prize for discovering the structure of DNA, has just published what can only be called a cancer manifesto in Open Biology. It's full of fairly harsh criticisms for current cancer researchers, but also suggests several ways forward in the "war on cancer." Among other claims, Watson asserts that antioxidants like vitamin C — often recommended as cancer-prevention supplements — could be causing some forms of cancer. He also has harsh words for personalized medicine, and the laziness of cancer researchers.

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Watson, now in his 80s, has spent a great deal of his life raising money to fund cancer research at Cold Spring Harbor Laboratory, where he's served as director since the late 1960s. Clearly anticipating his own mortality, he mourns the lack of good leadership in cancer research:

That we now have no General of influence, much less power, say an Eisenhower or even better a Patton, leading our country's War on Cancer says everything. Needed soon is a leader that has our cancer drug development world working every day and all through the night.

He suggests that the problem is researchers are slacking, only putting in "never frantic, largely five-day working week[s]."

He goes on to say that the current craze for "personalized medicine" that will treat cancer is just not going to work. But the main problem comes from government money being misspent:

The now much-touted genome-based personal cancer therapies may turn out to be much less important tools for future medicine than the newspapers of today lead us to hope. Sending more government cancer monies towards innovative, anti-metastatic drug development to appropriate high-quality academic institutions would better use National Cancer Institute's (NCI) monies than the large sums spent now testing drugs for which we have little hope of true breakthroughs. The biggest obstacle today to moving forward effectively towards a true war against cancer may, in fact, come from the inherently conservative nature of today's cancer research establishments.

He goes on to say that conventional thinking about cancer is all wrong. Antioxidants may be undermining cancer therapies and even causing cancer:

In light of the recent data strongly hinting that much of late-stage cancer's untreatability may arise from its possession of too many antioxidants, the time has come to seriously ask whether antioxidant use much more likely causes than prevents cancer.

All in all, the by now vast number of nutritional intervention trials using the antioxidants β-carotene, vitamin A, vitamin C, vitamin E and selenium have shown no obvious effectiveness in preventing gastrointestinal cancer nor in lengthening mortality. In fact, they seem to slightly shorten the lives of those who take them. Future data may, in fact, show that antioxidant use, particularly that of vitamin E, leads to a small number of cancers that would not have come into existence but for antioxidant supplementation. Blueberries best be eaten because they taste good, not because their consumption will lead to less cancer.

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It is thought that antioxidants can prevent damage to DNA from oxygen radicals. But, argues Watson, we want oxygen radicals in cancer cells because this can cause the cells to die. Taking antioxidants might be preventing cancer drugs from destroying cancer cells. Instead, he recommends patients combine anti-antioxidants with cancer drugs.

Watson also recommends an area of research, into a class of proteins called RNAi, which can be used to shut down the activity of genes. He claims that we need less than a billion dollars to win the war on cancer if we focus on RNAi research:

The total sum of money required for RNAi methodologies to reveal the remaining major molecular targets for future anti-cancer drug development need not be more than 500–1000 million dollars. Unfortunately, the NCI now is unlikely to take on still one more big science project when it is so hard-pressed to fund currently funded cancer programmes ... Further financial backing, allowing many more cancer-focused academic institutions to also go big using RNAi-based target discovery as well as to let them go on to the early stages of subsequent drug discovery, is not beyond the might of the world's major government research funding bodies nor that of our world's many, many super billionaires. The main factor holding us back from overcoming most of metastatic cancer over the next decade may soon no longer be lack of knowledge but our world's increasing failure to intelligently direct its ‘monetary might' towards more human-society-benefiting directions.

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Watson also wants researchers to focus on a protein called Myc, which is believed to regulate the activity of 15% of our genes. Its activity is also linked to many kinds of cancer. Using RNAi methods, it's possible we could figure out a way to control Myc, and thus shut down pathways to cancer.

Further Reading:

Watson's manifesto, "Oxidants, antioxidants, and the current incurability of metastatic cancers," in Open Biology

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Reuters' Sharon Begley has a good report on what other cancer researchers think about Watson's comments.

DISCUSSION

Dr Emilio Lizardo

James Watson is far more intelligent than I am and clearly has an interest in this, yet he seems to understand little of how cancer works. Cancer is a disease of the chromosomes. Our cells are constantly dividing. In an effort to EXACTLY replicate 3 billion base pairs billions or trillions of times a day, some mistakes will be made. The vast, vast majority of these will either be harmless, fatal to the cell (also harmless) or detected by the bodies various native surveillance systems and destroyed. However, a very, very, very few will escape surveillance and confer an advantage on the cell it should not have. This is a cancer cell. That cell will do things it should not do - divide more rapidly, fail to die when it should, escape the containment systems of it's cell of origin, spread to places it should not be, make proteins it should not, cause other body systems to do things they should not, maybe more. That is cancer. The problem is, in almost all cancers, it isn't just one mutation. It is hundreds. Thousands. Maybe more. It has been suggested that a lung cancer has one mutation for each 15 cigarettes a person has ever smoked. 20 cigs/pack/day x 365 days/year x 30 years divided by 15 equals...oh my god. Many of these are harmless, but some are not. It is not much of an exaggeration to suggest that every single cancer is a different disease. All 200,000 cases of lung cancer found every year in this country are different diseases. All 200,000 breast cancers are different diseases. There are exceptions (Chronic myelogenous leukemia. Sort of) but not many. It gets worse. As the daughter cells of that one original cell divide, they accumulate new mutations. So each individual person's cancer may be several different diseases. This is why there is no "cure for cancer."

If you prefer cartoon form, this should help:

http://www.phdcomics.com/comics/archive.php?comicid=1162

myc is being researched extensively. It is only one of these pathways and a perfect example of why no one single line of research will cure all cancer.

iRNA is new to me and maybe it is a final common pathway that can be targeted, but to say that this is the answer to ALL cancers or that an answer is in our reach for "only" a billion dollars seems hopelessly naive, even if he is talking about 1962 dollars.

I worry about a lot of things, but becoming obsolete because of some miracle breakthrough is not one of them.